[{"publication_status":"published","_id":"13052","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"},{"_id":"NanoFab"}],"series_title":"MIMB","external_id":{"pmid":["37106180"]},"project":[{"name":"Cellular navigation along spatial gradients","call_identifier":"H2020","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"ec_funded":1,"abstract":[{"text":"Imaging of the immunological synapse (IS) between dendritic cells (DCs) and T cells in suspension is hampered by suboptimal alignment of cell-cell contacts along the vertical imaging plane. This requires optical sectioning that often results in unsatisfactory resolution in time and space. Here, we present a workflow where DCs and T cells are confined between a layer of glass and polydimethylsiloxane (PDMS) that orients the cells along one, horizontal imaging plane, allowing for fast en-face-imaging of the DC-T cell IS.","lang":"eng"}],"article_processing_charge":"No","alternative_title":["Methods in Molecular Biology"],"acknowledgement":"A.L. was funded by an Erwin Schrödinger postdoctoral fellowship of the Austrian Science Fund (FWF, project number: J4542-B) and is an EMBO non-stipendiary postdoctoral fellow. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. We thank the Imaging & Optics facility, the Nanofabrication facility, and the Miba Machine Shop of ISTA for their excellent support.","publication_identifier":{"isbn":["9781071631348"],"eissn":["1940-6029"],"issn":["1064-3745"],"eisbn":["9781071631355"]},"scopus_import":"1","year":"2023","type":"book_chapter","doi":"10.1007/978-1-0716-3135-5_9","pmid":1,"oa_version":"None","acknowledged_ssus":[{"_id":"Bio"},{"_id":"NanoFab"},{"_id":"M-Shop"}],"intvolume":"      2654","publication":"The Immune Synapse","publisher":"Springer Nature","quality_controlled":"1","page":"137-147","status":"public","title":"En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses","author":[{"orcid":"0000-0002-1073-744X","last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F"},{"full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","orcid":"0000-0001-5145-4609","first_name":"Jack"},{"first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"editor":[{"first_name":"Cosima","last_name":"Baldari","full_name":"Baldari, Cosima"},{"full_name":"Dustin, Michael","last_name":"Dustin","first_name":"Michael"}],"date_updated":"2023-10-17T08:44:53Z","citation":{"mla":"Leithner, Alexander F., et al. “En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses.” <i>The Immune Synapse</i>, edited by Cosima Baldari and Michael Dustin, vol. 2654, Springer Nature, 2023, pp. 137–47, doi:<a href=\"https://doi.org/10.1007/978-1-0716-3135-5_9\">10.1007/978-1-0716-3135-5_9</a>.","ama":"Leithner AF, Merrin J, Sixt MK. En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses. In: Baldari C, Dustin M, eds. <i>The Immune Synapse</i>. Vol 2654. MIMB. New York, NY: Springer Nature; 2023:137-147. doi:<a href=\"https://doi.org/10.1007/978-1-0716-3135-5_9\">10.1007/978-1-0716-3135-5_9</a>","ista":"Leithner AF, Merrin J, Sixt MK. 2023.En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses. In: The Immune Synapse. Methods in Molecular Biology, vol. 2654, 137–147.","chicago":"Leithner, Alexander F, Jack Merrin, and Michael K Sixt. “En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses.” In <i>The Immune Synapse</i>, edited by Cosima Baldari and Michael Dustin, 2654:137–47. MIMB. New York, NY: Springer Nature, 2023. <a href=\"https://doi.org/10.1007/978-1-0716-3135-5_9\">https://doi.org/10.1007/978-1-0716-3135-5_9</a>.","ieee":"A. F. Leithner, J. Merrin, and M. K. Sixt, “En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses,” in <i>The Immune Synapse</i>, vol. 2654, C. Baldari and M. Dustin, Eds. New York, NY: Springer Nature, 2023, pp. 137–147.","short":"A.F. Leithner, J. Merrin, M.K. Sixt, in:, C. Baldari, M. Dustin (Eds.), The Immune Synapse, Springer Nature, New York, NY, 2023, pp. 137–147.","apa":"Leithner, A. F., Merrin, J., &#38; Sixt, M. K. (2023). En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses. In C. Baldari &#38; M. Dustin (Eds.), <i>The Immune Synapse</i> (Vol. 2654, pp. 137–147). New York, NY: Springer Nature. <a href=\"https://doi.org/10.1007/978-1-0716-3135-5_9\">https://doi.org/10.1007/978-1-0716-3135-5_9</a>"},"day":"28","volume":2654,"place":"New York, NY","month":"04","date_created":"2023-05-22T08:41:48Z","date_published":"2023-04-28T00:00:00Z"},{"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"issue":"1","publication":"Developmental Cell","intvolume":"        57","quality_controlled":"1","page":"47-62.e9","main_file_link":[{"open_access":"1","url":"https://www.sciencedirect.com/science/article/pii/S1534580721009497"}],"publisher":"Cell Press ; Elsevier","status":"public","title":"WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues","author":[{"last_name":"Gaertner","first_name":"Florian","full_name":"Gaertner, Florian"},{"full_name":"Reis-Rodrigues, Patricia","first_name":"Patricia","last_name":"Reis-Rodrigues"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid","first_name":"Ingrid","last_name":"De Vries"},{"id":"4167FE56-F248-11E8-B48F-1D18A9856A87","full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","last_name":"Hons","first_name":"Miroslav"},{"last_name":"Aguilera","first_name":"Juan","full_name":"Aguilera, Juan"},{"first_name":"Michael","orcid":"0000-0003-4844-6311","last_name":"Riedl","full_name":"Riedl, Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X","first_name":"Alexander F"},{"full_name":"Tasciyan, Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","last_name":"Tasciyan","first_name":"Saren"},{"last_name":"Kopf","orcid":"0000-0002-2187-6656","first_name":"Aglaja","full_name":"Kopf, Aglaja","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jack","last_name":"Merrin","orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Zheden, Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","first_name":"Vanessa","last_name":"Zheden","orcid":"0000-0002-9438-4783"},{"full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","last_name":"Kaufmann","first_name":"Walter"},{"first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","first_name":"Michael K"}],"oa":1,"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12726"},{"status":"public","relation":"dissertation_contains","id":"14530"},{"status":"public","relation":"dissertation_contains","id":"12401"}]},"date_updated":"2024-03-25T23:30:12Z","day":"10","citation":{"mla":"Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” <i>Developmental Cell</i>, vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">10.1016/j.devcel.2021.11.024</a>.","ista":"Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK. 2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 57(1), 47–62.e9.","ama":"Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. <i>Developmental Cell</i>. 2022;57(1):47-62.e9. doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">10.1016/j.devcel.2021.11.024</a>","chicago":"Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons, Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” <i>Developmental Cell</i>. Cell Press ; Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">https://doi.org/10.1016/j.devcel.2021.11.024</a>.","ieee":"F. Gaertner <i>et al.</i>, “WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues,” <i>Developmental Cell</i>, vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022.","apa":"Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl, M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. <i>Developmental Cell</i>. Cell Press ; Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">https://doi.org/10.1016/j.devcel.2021.11.024</a>","short":"F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl, A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild, M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9."},"volume":57,"article_type":"original","month":"01","date_created":"2022-01-30T23:01:33Z","date_published":"2022-01-10T00:00:00Z","language":[{"iso":"eng"}],"_id":"10703","publication_status":"published","ddc":["570"],"department":[{"_id":"MiSi"},{"_id":"EM-Fac"},{"_id":"NanoFab"},{"_id":"BjHo"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020","grant_number":"747687","_id":"260AA4E2-B435-11E9-9278-68D0E5697425"},{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"724373","name":"Cellular navigation along spatial gradients"}],"external_id":{"pmid":["34919802"],"isi":["000768933800005"]},"ec_funded":1,"abstract":[{"lang":"eng","text":"When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes."}],"article_processing_charge":"No","acknowledgement":"We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll for advice on fluorescent labeling of collagen gels. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron Microscopy Facility. This work was funded by grants from the European Research Council ( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 747687.","publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"isi":1,"type":"journal_article","year":"2022","scopus_import":"1","doi":"10.1016/j.devcel.2021.11.024","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"pmid":1,"oa_version":"Published Version"},{"isi":1,"year":"2022","type":"journal_article","scopus_import":"1","doi":"10.7554/eLife.78995","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"oa_version":"Published Version","_id":"11843","language":[{"iso":"eng"}],"publication_status":"published","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"MiSi"},{"_id":"CaGu"}],"project":[{"call_identifier":"H2020","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular navigation along spatial gradients"},{"_id":"26018E70-B435-11E9-9278-68D0E5697425","grant_number":"P29911","call_identifier":"FWF","name":"Mechanical adaptation of lamellipodial actin"}],"external_id":{"isi":["000838410200001"]},"ec_funded":1,"abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","article_processing_charge":"Yes","file_date_updated":"2022-08-16T08:57:37Z","publication_identifier":{"eissn":["2050-084X"]},"related_material":{"record":[{"status":"public","relation":"earlier_version","id":"10316"}]},"date_updated":"2023-08-03T12:54:21Z","day":"26","citation":{"ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022).","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>, vol. 11, e78995, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>."},"file":[{"checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","date_updated":"2022-08-16T08:57:37Z","file_name":"2022_eLife_Tomasek.pdf","success":1,"content_type":"application/pdf","access_level":"open_access","file_size":2057577,"relation":"main_file","creator":"cchlebak","file_id":"11861","date_created":"2022-08-16T08:57:37Z"}],"volume":11,"article_type":"original","has_accepted_license":"1","month":"07","date_published":"2022-07-26T00:00:00Z","date_created":"2022-08-14T22:01:46Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"publication":"eLife","intvolume":"        11","quality_controlled":"1","publisher":"eLife Sciences Publications","status":"public","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","article_number":"e78995","author":[{"id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","full_name":"Tomasek, Kathrin","last_name":"Tomasek","first_name":"Kathrin"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","first_name":"Alexander F","last_name":"Leithner"},{"full_name":"Glatzová, Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","first_name":"Ivana","last_name":"Glatzová"},{"first_name":"Michael S.","last_name":"Lukesch","full_name":"Lukesch, Michael S."},{"last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sixt","orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"oa":1},{"department":[{"_id":"MiSi"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"isi":["000626365700001"],"pmid":["33533935"]},"publication_status":"published","ddc":["570"],"_id":"9094","language":[{"iso":"eng"}],"article_processing_charge":"No","publication_identifier":{"issn":["0021-9525"],"eissn":["1540-8140"]},"file_date_updated":"2022-05-12T14:16:21Z","abstract":[{"text":"Dendritic cells (DCs) are crucial for the priming of naive T cells and the initiation of adaptive immunity. Priming is initiated at a heterologous cell–cell contact, the immunological synapse (IS). While it is established that F-actin dynamics regulates signaling at the T cell side of the contact, little is known about the cytoskeletal contribution on the DC side. Here, we show that the DC actin cytoskeleton is decisive for the formation of a multifocal synaptic structure, which correlates with T cell priming efficiency. DC actin at the IS appears in transient foci that are dynamized by the WAVE regulatory complex (WRC). The absence of the WRC in DCs leads to stabilized contacts with T cells, caused by an increase in ICAM1-integrin–mediated cell–cell adhesion. This results in lower numbers of activated and proliferating T cells, demonstrating an important role for DC actin in the regulation of immune synapse functionality.","lang":"eng"}],"scopus_import":"1","type":"journal_article","isi":1,"year":"2021","pmid":1,"oa_version":"Published Version","doi":"10.1083/jcb.202006081","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","short":"CC BY-NC-SA (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png"},"intvolume":"       220","publication":"Journal of Cell Biology","publisher":"Rockefeller University Press","quality_controlled":"1","issue":"4","author":[{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","orcid":"0000-0002-1073-744X","first_name":"Alexander F"},{"full_name":"Altenburger, LM","last_name":"Altenburger","first_name":"LM"},{"first_name":"R","last_name":"Hauschild","full_name":"Hauschild, R"},{"id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","full_name":"Assen, Frank P","first_name":"Frank P","orcid":"0000-0003-3470-6119","last_name":"Assen"},{"full_name":"Rottner, K","first_name":"K","last_name":"Rottner"},{"last_name":"TEB","first_name":"Stradal","full_name":"TEB, Stradal"},{"last_name":"Diz-Muñoz","first_name":"A","full_name":"Diz-Muñoz, A"},{"last_name":"Stein","first_name":"JV","full_name":"Stein, JV"},{"orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"oa":1,"status":"public","article_number":"e202006081","title":"Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse","date_updated":"2023-09-05T13:57:53Z","file":[{"date_updated":"2022-05-12T14:16:21Z","success":1,"file_name":"2021_JournCellBiology_Leithner.pdf","checksum":"843ebc153847c8626e13c9c5ce71d533","file_size":5102328,"creator":"dernst","file_id":"11367","relation":"main_file","date_created":"2022-05-12T14:16:21Z","content_type":"application/pdf","access_level":"open_access"}],"citation":{"chicago":"Leithner, Alexander F, LM Altenburger, R Hauschild, Frank P Assen, K Rottner, Stradal TEB, A Diz-Muñoz, JV Stein, and Michael K Sixt. “Dendritic Cell Actin Dynamics Control Contact Duration and Priming Efficiency at the Immunological Synapse.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2021. <a href=\"https://doi.org/10.1083/jcb.202006081\">https://doi.org/10.1083/jcb.202006081</a>.","ista":"Leithner AF, Altenburger L, Hauschild R, Assen FP, Rottner K, TEB S, Diz-Muñoz A, Stein J, Sixt MK. 2021. Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. Journal of Cell Biology. 220(4), e202006081.","ama":"Leithner AF, Altenburger L, Hauschild R, et al. Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. <i>Journal of Cell Biology</i>. 2021;220(4). doi:<a href=\"https://doi.org/10.1083/jcb.202006081\">10.1083/jcb.202006081</a>","mla":"Leithner, Alexander F., et al. “Dendritic Cell Actin Dynamics Control Contact Duration and Priming Efficiency at the Immunological Synapse.” <i>Journal of Cell Biology</i>, vol. 220, no. 4, e202006081, Rockefeller University Press, 2021, doi:<a href=\"https://doi.org/10.1083/jcb.202006081\">10.1083/jcb.202006081</a>.","short":"A.F. Leithner, L. Altenburger, R. Hauschild, F.P. Assen, K. Rottner, S. TEB, A. Diz-Muñoz, J. Stein, M.K. Sixt, Journal of Cell Biology 220 (2021).","apa":"Leithner, A. F., Altenburger, L., Hauschild, R., Assen, F. P., Rottner, K., TEB, S., … Sixt, M. K. (2021). Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.202006081\">https://doi.org/10.1083/jcb.202006081</a>","ieee":"A. F. Leithner <i>et al.</i>, “Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse,” <i>Journal of Cell Biology</i>, vol. 220, no. 4. Rockefeller University Press, 2021."},"day":"05","month":"04","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","date_published":"2021-04-05T00:00:00Z","date_created":"2021-02-05T10:08:04Z","article_type":"original","volume":220,"has_accepted_license":"1"},{"author":[{"id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","full_name":"Tomasek, Kathrin","last_name":"Tomasek","orcid":"0000-0003-3768-877X","first_name":"Kathrin"},{"first_name":"Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Glatzová","first_name":"Ivana","full_name":"Glatzová, Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d"},{"last_name":"Lukesch","first_name":"Michael S.","full_name":"Lukesch, Michael S."},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"last_name":"Sixt","orcid":"0000-0002-4561-241X","first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S.","oa":1,"ec_funded":1,"status":"public","abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","publication":"bioRxiv","department":[{"_id":"CaGu"},{"_id":"MiSi"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","project":[{"grant_number":"724373","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular navigation along spatial gradients"},{"_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P29911","name":"Mechanical adaptation of lamellipodial actin"}],"main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1"}],"publisher":"Cold Spring Harbor Laboratory","_id":"10316","language":[{"iso":"eng"}],"publication_status":"submitted","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"month":"10","date_published":"2021-10-18T00:00:00Z","date_created":"2021-11-19T12:24:16Z","oa_version":"Preprint","doi":"10.1101/2021.10.18.464770","date_updated":"2024-03-25T23:30:19Z","citation":{"ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>.","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, <a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>"},"day":"18","related_material":{"record":[{"status":"public","relation":"later_version","id":"11843"},{"status":"public","id":"10307","relation":"dissertation_contains"}]},"year":"2021","type":"preprint"},{"oa_version":"Published Version","doi":"10.15479/AT:ISTA:th_998","publist_id":"7542","supervisor":[{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","orcid":"0000-0002-6620-9179","first_name":"Michael K"}],"tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"pubrep_id":"998","type":"dissertation","year":"2018","acknowledgement":"First of all I would like to thank Michael Sixt for giving me the opportunity to work in \r\nhis group and for his support throughout the years. He is a truly inspiring person and \r\nthe  best  boss  one  can  imagine.  I  would  also  like  to  thank  all  current  and  past \r\nmembers of the Sixt group for their help and the great working atmosphere in the lab. \r\nIt is a true privilege to work with such a bright, funny and friendly group of people and \r\nI’m  proud  that  I  could  be  part  of  it.  Furthermore,  I  would  like  to  say  ‘thank  you’  to Daria Siekhaus for all the meetings and discussion we had throughout the years \r\nand to  Federica  Benvenuti  for  being  part  of  my  committee.  I  am  also  grateful  to  Jack \r\nMerrin  in  the  nanofabrication  facility  and  all  the  people  working  in  the  bioimaging-\r\n, the electron microscopy- and the preclinical facilities.","article_processing_charge":"No","alternative_title":["ISTA Thesis"],"file_date_updated":"2021-02-11T23:30:17Z","publication_identifier":{"issn":["2663-337X"]},"abstract":[{"text":"In the here presented thesis, we explore the role of branched actin networks in cell migration and antigen presentation, the two most relevant processes in dendritic cell biology. Branched actin networks construct lamellipodial protrusions at the leading edge of migrating cells. These are typically seen as adhesive structures, which mediate force transduction to the extracellular matrix that leads to forward locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found that the resulting cells lack lamellipodial protrusions. Instead, depending on the maturation state, one or multiple filopodia were formed. By challenging these cells in a variety of migration assays we found that lamellipodial protrusions are dispensable for the locomotion of leukocytes and actually dampen the speed of migration. However, lamellipodia are critically required to negotiate complex environments that DCs experience while they travel to the next draining lymph node. Taken together our results suggest that leukocyte lamellipodia have rather a sensory- than a force transducing function. Furthermore, we show for the first time structure and dynamics of dendritic cell F-actin at the immunological synapse with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension, leading to an altered ultrastructure of the immunological synapse and severe T cell priming defects. These results point towards a previously unappreciated role of the cellular mechanics of dendritic cells in T cell activation. Additionally, we present a novel cell culture based system for the differentiation of dendritic cells from conditionally immortalized hematopoietic precursors. These precursor cells are genetically tractable via the CRISPR/Cas9 system while they retain their ability to differentiate into highly migratory dendritic cells and other immune cells. This will foster the study of all aspects of dendritic cell biology and beyond. ","lang":"eng"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"MiSi"}],"_id":"323","language":[{"iso":"eng"}],"ddc":["571","599","610"],"publication_status":"published","month":"04","date_created":"2018-12-11T11:45:49Z","date_published":"2018-04-12T00:00:00Z","degree_awarded":"PhD","has_accepted_license":"1","date_updated":"2023-09-07T12:39:44Z","citation":{"mla":"Leithner, Alexander F. <i>Branched Actin Networks in Dendritic Cell Biology</i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">10.15479/AT:ISTA:th_998</a>.","ama":"Leithner AF. Branched actin networks in dendritic cell biology. 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">10.15479/AT:ISTA:th_998</a>","ista":"Leithner AF. 2018. Branched actin networks in dendritic cell biology. Institute of Science and Technology Austria.","chicago":"Leithner, Alexander F. “Branched Actin Networks in Dendritic Cell Biology.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">https://doi.org/10.15479/AT:ISTA:th_998</a>.","ieee":"A. F. Leithner, “Branched actin networks in dendritic cell biology,” Institute of Science and Technology Austria, 2018.","short":"A.F. Leithner, Branched Actin Networks in Dendritic Cell Biology, Institute of Science and Technology Austria, 2018.","apa":"Leithner, A. F. (2018). <i>Branched actin networks in dendritic cell biology</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">https://doi.org/10.15479/AT:ISTA:th_998</a>"},"day":"12","file":[{"date_created":"2019-04-05T09:23:11Z","embargo_to":"open_access","file_id":"6219","relation":"source_file","creator":"dernst","file_size":29027671,"access_level":"closed","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"PhD_thesis_AlexLeithner_final_version.docx","date_updated":"2021-02-11T23:30:17Z","checksum":"d5e3edbac548c26c1fa43a4b37a54a4c"},{"checksum":"071f7476db29e41146824ebd0697cb10","embargo":"2019-04-15","date_updated":"2021-02-11T11:17:16Z","file_name":"PhD_thesis_AlexLeithner.pdf","content_type":"application/pdf","access_level":"open_access","creator":"dernst","file_id":"6220","relation":"main_file","file_size":66045341,"date_created":"2019-04-05T09:23:11Z"}],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"1321"}]},"author":[{"orcid":"0000-0002-1073-744X","last_name":"Leithner","first_name":"Alexander F","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"status":"public","title":"Branched actin networks in dendritic cell biology","page":"99","publisher":"Institute of Science and Technology Austria","acknowledged_ssus":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}]},{"abstract":[{"lang":"eng","text":"Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux."}],"ec_funded":1,"acknowledgement":"This work was funded by grants from the European Research Council (ERC StG 281556 and CoG 724373) and the Austrian Science Foundation (FWF) to M.S. and by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457 and CR23I3_156234 to J.V.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687, and J.R. was funded by an EMBO long-term fellowship (ALTF 1396-2014).","article_processing_charge":"No","language":[{"iso":"eng"}],"_id":"15","publication_status":"published","project":[{"name":"Cellular navigation along spatial gradients","grant_number":"724373","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"747687"},{"_id":"25A48D24-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1396-2014","name":"Molecular and system level view of immune cell migration"},{"call_identifier":"FP7","grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"}],"external_id":{"isi":["000433041500026"],"pmid":["29777221"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"MiSi"},{"_id":"Bio"}],"publist_id":"8040","doi":"10.1038/s41590-018-0109-z","oa_version":"Published Version","pmid":1,"isi":1,"year":"2018","type":"journal_article","scopus_import":"1","title":"Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells","status":"public","oa":1,"author":[{"last_name":"Hons","orcid":"0000-0002-6625-3348","first_name":"Miroslav","full_name":"Hons, Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87"},{"id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","full_name":"Kopf, Aglaja","first_name":"Aglaja","last_name":"Kopf","orcid":"0000-0002-2187-6656"},{"first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert"},{"first_name":"Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F"},{"last_name":"Gärtner","orcid":"0000-0001-6120-3723","first_name":"Florian R","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","full_name":"Gärtner, Florian R"},{"full_name":"Abe, Jun","last_name":"Abe","first_name":"Jun"},{"last_name":"Renkawitz","orcid":"0000-0003-2856-3369","first_name":"Jörg","full_name":"Renkawitz, Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Stein","first_name":"Jens","full_name":"Stein, Jens"},{"first_name":"Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"acknowledged_ssus":[{"_id":"SSU"}],"issue":"6","page":"606 - 616","quality_controlled":"1","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pubmed/29777221","open_access":"1"}],"publisher":"Nature Publishing Group","publication":"Nature Immunology","intvolume":"        19","volume":19,"date_published":"2018-05-18T00:00:00Z","date_created":"2018-12-11T11:44:10Z","month":"05","related_material":{"record":[{"status":"public","id":"6891","relation":"dissertation_contains"}]},"citation":{"ieee":"M. Hons <i>et al.</i>, “Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells,” <i>Nature Immunology</i>, vol. 19, no. 6. Nature Publishing Group, pp. 606–616, 2018.","apa":"Hons, M., Kopf, A., Hauschild, R., Leithner, A. F., Gärtner, F. R., Abe, J., … Sixt, M. K. (2018). Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. <i>Nature Immunology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41590-018-0109-z\">https://doi.org/10.1038/s41590-018-0109-z</a>","short":"M. Hons, A. Kopf, R. Hauschild, A.F. Leithner, F.R. Gärtner, J. Abe, J. Renkawitz, J. Stein, M.K. Sixt, Nature Immunology 19 (2018) 606–616.","mla":"Hons, Miroslav, et al. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” <i>Nature Immunology</i>, vol. 19, no. 6, Nature Publishing Group, 2018, pp. 606–16, doi:<a href=\"https://doi.org/10.1038/s41590-018-0109-z\">10.1038/s41590-018-0109-z</a>.","ista":"Hons M, Kopf A, Hauschild R, Leithner AF, Gärtner FR, Abe J, Renkawitz J, Stein J, Sixt MK. 2018. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 19(6), 606–616.","ama":"Hons M, Kopf A, Hauschild R, et al. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. <i>Nature Immunology</i>. 2018;19(6):606-616. doi:<a href=\"https://doi.org/10.1038/s41590-018-0109-z\">10.1038/s41590-018-0109-z</a>","chicago":"Hons, Miroslav, Aglaja Kopf, Robert Hauschild, Alexander F Leithner, Florian R Gärtner, Jun Abe, Jörg Renkawitz, Jens Stein, and Michael K Sixt. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” <i>Nature Immunology</i>. Nature Publishing Group, 2018. <a href=\"https://doi.org/10.1038/s41590-018-0109-z\">https://doi.org/10.1038/s41590-018-0109-z</a>."},"day":"18","date_updated":"2024-03-25T23:30:22Z"},{"abstract":[{"lang":"eng","text":"Cells migrating in multicellular organisms steadily traverse complex three-dimensional (3D) environments. To decipher the underlying cell biology, current experimental setups either use simplified 2D, tissue-mimetic 3D (e.g., collagen matrices) or in vivo environments. While only in vivo experiments are truly physiological, they do not allow for precise manipulation of environmental parameters. 2D in vitro experiments do allow mechanical and chemical manipulations, but increasing evidence demonstrates substantial differences of migratory mechanisms in 2D and 3D. Here, we describe simple, robust, and versatile “pillar forests” to investigate cell migration in complex but fully controllable 3D environments. Pillar forests are polydimethylsiloxane-based setups, in which two closely adjacent surfaces are interconnected by arrays of micrometer-sized pillars. Changing the pillar shape, size, height and the inter-pillar distance precisely manipulates microenvironmental parameters (e.g., pore sizes, micro-geometry, micro-topology), while being easily combined with chemotactic cues, surface coatings, diverse cell types and advanced imaging techniques. Thus, pillar forests combine the advantages of 2D cell migration assays with the precise definition of 3D environmental parameters."}],"article_processing_charge":"No","publication_identifier":{"issn":["0091679X"]},"_id":"153","language":[{"iso":"eng"}],"publication_status":"published","department":[{"_id":"MiSi"},{"_id":"NanoFab"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"pmid":["30165964"],"isi":["000452412300006"]},"publist_id":"7768","doi":"10.1016/bs.mcb.2018.07.004","pmid":1,"oa_version":"None","isi":1,"year":"2018","type":"book_chapter","scopus_import":"1","status":"public","title":"Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments","author":[{"orcid":"0000-0003-2856-3369","last_name":"Renkawitz","first_name":"Jörg","full_name":"Renkawitz, Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Reversat, Anne","id":"35B76592-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0666-8928","last_name":"Reversat","first_name":"Anne"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","first_name":"Alexander F","orcid":"0000-0002-1073-744X","last_name":"Leithner"},{"full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","first_name":"Jack","last_name":"Merrin","orcid":"0000-0001-5145-4609"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179"}],"publication":"Methods in Cell Biology","intvolume":"       147","quality_controlled":"1","page":"79 - 91","publisher":"Academic Press","volume":147,"month":"07","date_created":"2018-12-11T11:44:54Z","date_published":"2018-07-27T00:00:00Z","date_updated":"2023-09-13T08:56:35Z","day":"27","citation":{"chicago":"Renkawitz, Jörg, Anne Reversat, Alexander F Leithner, Jack Merrin, and Michael K Sixt. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in Complex but Controlled 3D Environments.” In <i>Methods in Cell Biology</i>, 147:79–91. Academic Press, 2018. <a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">https://doi.org/10.1016/bs.mcb.2018.07.004</a>.","ama":"Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In: <i>Methods in Cell Biology</i>. Vol 147. Academic Press; 2018:79-91. doi:<a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">10.1016/bs.mcb.2018.07.004</a>","ista":"Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. 2018.Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In: Methods in Cell Biology. vol. 147, 79–91.","mla":"Renkawitz, Jörg, et al. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in Complex but Controlled 3D Environments.” <i>Methods in Cell Biology</i>, vol. 147, Academic Press, 2018, pp. 79–91, doi:<a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">10.1016/bs.mcb.2018.07.004</a>.","short":"J. Renkawitz, A. Reversat, A.F. Leithner, J. Merrin, M.K. Sixt, in:, Methods in Cell Biology, Academic Press, 2018, pp. 79–91.","apa":"Renkawitz, J., Reversat, A., Leithner, A. F., Merrin, J., &#38; Sixt, M. K. (2018). Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In <i>Methods in Cell Biology</i> (Vol. 147, pp. 79–91). Academic Press. <a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">https://doi.org/10.1016/bs.mcb.2018.07.004</a>","ieee":"J. Renkawitz, A. Reversat, A. F. Leithner, J. Merrin, and M. K. Sixt, “Micro-engineered ‘pillar forests’ to study cell migration in complex but controlled 3D environments,” in <i>Methods in Cell Biology</i>, vol. 147, Academic Press, 2018, pp. 79–91."}},{"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"6947"}]},"date_updated":"2024-03-25T23:30:05Z","day":"23","citation":{"apa":"Brown, M., Assen, F. P., Leithner, A. F., Abe, J., Schachner, H., Asfour, G., … Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.aal3662\">https://doi.org/10.1126/science.aal3662</a>","short":"M. Brown, F.P. Assen, A.F. Leithner, J. Abe, H. Schachner, G. Asfour, Z. Bagó Horváth, J. Stein, P. Uhrin, M.K. Sixt, D. Kerjaschki, Science 359 (2018) 1408–1411.","ieee":"M. Brown <i>et al.</i>, “Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice,” <i>Science</i>, vol. 359, no. 6382. American Association for the Advancement of Science, pp. 1408–1411, 2018.","ama":"Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. <i>Science</i>. 2018;359(6382):1408-1411. doi:<a href=\"https://doi.org/10.1126/science.aal3662\">10.1126/science.aal3662</a>","ista":"Brown M, Assen FP, Leithner AF, Abe J, Schachner H, Asfour G, Bagó Horváth Z, Stein J, Uhrin P, Sixt MK, Kerjaschki D. 2018. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 359(6382), 1408–1411.","mla":"Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” <i>Science</i>, vol. 359, no. 6382, American Association for the Advancement of Science, 2018, pp. 1408–11, doi:<a href=\"https://doi.org/10.1126/science.aal3662\">10.1126/science.aal3662</a>.","chicago":"Brown, Markus, Frank P Assen, Alexander F Leithner, Jun Abe, Helga Schachner, Gabriele Asfour, Zsuzsanna Bagó Horváth, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” <i>Science</i>. American Association for the Advancement of Science, 2018. <a href=\"https://doi.org/10.1126/science.aal3662\">https://doi.org/10.1126/science.aal3662</a>."},"article_type":"original","volume":359,"month":"03","date_created":"2018-12-11T11:46:16Z","date_published":"2018-03-23T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"}],"issue":"6382","publication":"Science","intvolume":"       359","quality_controlled":"1","page":"1408 - 1411","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1126/science.aal3662"}],"publisher":"American Association for the Advancement of Science","status":"public","title":"Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice","author":[{"first_name":"Markus","last_name":"Brown","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Assen, Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","first_name":"Frank P","last_name":"Assen","orcid":"0000-0003-3470-6119"},{"last_name":"Leithner","orcid":"0000-0002-1073-744X","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F"},{"last_name":"Abe","first_name":"Jun","full_name":"Abe, Jun"},{"full_name":"Schachner, Helga","first_name":"Helga","last_name":"Schachner"},{"last_name":"Asfour","first_name":"Gabriele","full_name":"Asfour, Gabriele"},{"full_name":"Bagó Horváth, Zsuzsanna","last_name":"Bagó Horváth","first_name":"Zsuzsanna"},{"full_name":"Stein, Jens","last_name":"Stein","first_name":"Jens"},{"last_name":"Uhrin","first_name":"Pavel","full_name":"Uhrin, Pavel"},{"orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"},{"full_name":"Kerjaschki, Dontscho","first_name":"Dontscho","last_name":"Kerjaschki"}],"oa":1,"type":"journal_article","isi":1,"year":"2018","scopus_import":"1","publist_id":"7428","doi":"10.1126/science.aal3662","pmid":1,"oa_version":"Published Version","_id":"402","language":[{"iso":"eng"}],"publication_status":"published","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"MiSi"}],"project":[{"name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Y 564-B12"},{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","grant_number":"281556","call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425"}],"external_id":{"pmid":["29567714"],"isi":["000428043600047"]},"ec_funded":1,"abstract":[{"text":"During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined.","lang":"eng"}],"article_processing_charge":"No","acknowledgement":"M.B. was supported by the Cell Communication in Health and Disease graduate study program of the Austrian Science Fund (FWF) and the Medical University of Vienna. M.S. was supported by the European Research Council (grant ERC GA 281556) and an FWF START award.\r\nWe thank C. Moussion for establishing the intralymphatic injection at IST Austria and for providing anti-PNAd hybridoma supernatant, R. Förster and A. Braun for sharing the intralymphatic injection technology, K. Vaahtomeri for the lentiviral constructs, M. Hons for establishing in vivo multiphoton imaging, the Sixt lab for intellectual input, M. Schunn for help with the design of the in vivo experiments, F. Langer for technical assistance with the in vivo experiments, the bioimaging facility of IST Austria for support, and R. Efferl for providing the CT26 cell line."},{"date_updated":"2023-09-11T14:01:18Z","file":[{"checksum":"9d5b74cd016505aeb9a4c2d33bbedaeb","file_name":"IST-2018-1067-v1+2_Leithner_et_al-2018-European_Journal_of_Immunology.pdf","date_updated":"2020-07-14T12:46:27Z","access_level":"open_access","content_type":"application/pdf","date_created":"2018-12-12T10:13:56Z","file_size":590106,"creator":"system","file_id":"5044","relation":"main_file"}],"citation":{"short":"A.F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, M.K. Sixt, European Journal of Immunology 48 (2018) 1074–1077.","apa":"Leithner, A. F., Renkawitz, J., de Vries, I., Hauschild, R., Haecker, H., &#38; Sixt, M. K. (2018). Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. <i>European Journal of Immunology</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1002/eji.201747358\">https://doi.org/10.1002/eji.201747358</a>","ieee":"A. F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, and M. K. Sixt, “Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration,” <i>European Journal of Immunology</i>, vol. 48, no. 6. Wiley-Blackwell, pp. 1074–1077, 2018.","ista":"Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. 2018. Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. European Journal of Immunology. 48(6), 1074–1077.","ama":"Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. <i>European Journal of Immunology</i>. 2018;48(6):1074-1077. doi:<a href=\"https://doi.org/10.1002/eji.201747358\">10.1002/eji.201747358</a>","mla":"Leithner, Alexander F., et al. “Fast and Efficient Genetic Engineering of Hematopoietic Precursor Cells for the Study of Dendritic Cell Migration.” <i>European Journal of Immunology</i>, vol. 48, no. 6, Wiley-Blackwell, 2018, pp. 1074–77, doi:<a href=\"https://doi.org/10.1002/eji.201747358\">10.1002/eji.201747358</a>.","chicago":"Leithner, Alexander F, Jörg Renkawitz, Ingrid de Vries, Robert Hauschild, Hans Haecker, and Michael K Sixt. “Fast and Efficient Genetic Engineering of Hematopoietic Precursor Cells for the Study of Dendritic Cell Migration.” <i>European Journal of Immunology</i>. Wiley-Blackwell, 2018. <a href=\"https://doi.org/10.1002/eji.201747358\">https://doi.org/10.1002/eji.201747358</a>."},"day":"13","volume":48,"has_accepted_license":"1","month":"02","date_published":"2018-02-13T00:00:00Z","license":"https://creativecommons.org/licenses/by-nc/4.0/","date_created":"2018-12-11T11:46:28Z","issue":"6","acknowledged_ssus":[{"_id":"SSU"}],"intvolume":"        48","publication":"European Journal of Immunology","publisher":"Wiley-Blackwell","quality_controlled":"1","page":"1074 - 1077","status":"public","title":"Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration","author":[{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","orcid":"0000-0002-1073-744X","first_name":"Alexander F"},{"id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","full_name":"Renkawitz, Jörg","first_name":"Jörg","last_name":"Renkawitz","orcid":"0000-0003-2856-3369"},{"last_name":"De Vries","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","last_name":"Hauschild","first_name":"Robert"},{"full_name":"Haecker, Hans","last_name":"Haecker","first_name":"Hans"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","first_name":"Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt"}],"oa":1,"scopus_import":"1","isi":1,"type":"journal_article","year":"2018","pubrep_id":"1067","doi":"10.1002/eji.201747358","publist_id":"7386","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png"},"oa_version":"Published Version","ddc":["570"],"publication_status":"published","_id":"437","language":[{"iso":"eng"}],"department":[{"_id":"MiSi"},{"_id":"Bio"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"isi":["000434963700016"]},"project":[{"name":"Cellular navigation along spatial gradients","call_identifier":"H2020","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"ec_funded":1,"abstract":[{"text":"Dendritic cells (DCs) are sentinels of the adaptive immune system that reside in peripheral organs of mammals. Upon pathogen encounter, they undergo maturation and up-regulate the chemokine receptor CCR7 that guides them along gradients of its chemokine ligands CCL19 and 21 to the next draining lymph node. There, DCs present peripherally acquired antigen to naïve T cells, thereby triggering adaptive immunity.","lang":"eng"}],"article_processing_charge":"Yes (via OA deal)","acknowledgement":"This work was supported by grants of the European Research Council (ERC CoG 724373) and the Austrian Science Fund (FWF) to M.S. We thank the scientific support units at IST Austria for excellent technical support.\r\nWe thank the  scientific  support units at IST Austria for excellent technical support.   ","file_date_updated":"2020-07-14T12:46:27Z"},{"issue":"5","publication":"Cell Reports","intvolume":"        19","page":"902 - 909","quality_controlled":"1","publisher":"Cell Press","status":"public","title":"Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia","author":[{"first_name":"Kari","orcid":"0000-0001-7829-3518","last_name":"Vaahtomeri","id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari"},{"first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus"},{"orcid":"0000-0001-9843-3522","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"De Vries"},{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F","last_name":"Leithner"},{"first_name":"Matthias","orcid":"0000-0001-8599-1226","last_name":"Mehling","full_name":"Mehling, Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","full_name":"Kaufmann, Walter","first_name":"Walter","last_name":"Kaufmann","orcid":"0000-0001-9735-5315"},{"first_name":"Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"date_updated":"2023-02-23T12:50:09Z","citation":{"chicago":"Vaahtomeri, Kari, Markus Brown, Robert Hauschild, Ingrid de Vries, Alexander F Leithner, Matthias Mehling, Walter Kaufmann, and Michael K Sixt. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” <i>Cell Reports</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>.","ista":"Vaahtomeri K, Brown M, Hauschild R, de Vries I, Leithner AF, Mehling M, Kaufmann W, Sixt MK. 2017. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Reports. 19(5), 902–909.","ama":"Vaahtomeri K, Brown M, Hauschild R, et al. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. <i>Cell Reports</i>. 2017;19(5):902-909. doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>","mla":"Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” <i>Cell Reports</i>, vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>.","apa":"Vaahtomeri, K., Brown, M., Hauschild, R., de Vries, I., Leithner, A. F., Mehling, M., … Sixt, M. K. (2017). Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>","short":"K. Vaahtomeri, M. Brown, R. Hauschild, I. de Vries, A.F. Leithner, M. Mehling, W. Kaufmann, M.K. Sixt, Cell Reports 19 (2017) 902–909.","ieee":"K. Vaahtomeri <i>et al.</i>, “Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia,” <i>Cell Reports</i>, vol. 19, no. 5. Cell Press, pp. 902–909, 2017."},"day":"02","file":[{"access_level":"open_access","content_type":"application/pdf","date_created":"2018-12-12T10:14:54Z","file_size":2248814,"file_id":"5109","relation":"main_file","creator":"system","checksum":"8fdddaab1f1d76a6ec9ca94dcb6b07a2","file_name":"IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf","date_updated":"2020-07-14T12:47:38Z"}],"volume":19,"has_accepted_license":"1","month":"05","date_published":"2017-05-02T00:00:00Z","date_created":"2018-12-11T11:47:50Z","_id":"672","language":[{"iso":"eng"}],"publication_status":"published","ddc":["570"],"department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","project":[{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"281556"},{"name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","call_identifier":"FWF","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"ec_funded":1,"abstract":[{"lang":"eng","text":"Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration."}],"article_processing_charge":"Yes","file_date_updated":"2020-07-14T12:47:38Z","publication_identifier":{"issn":["22111247"]},"year":"2017","type":"journal_article","scopus_import":1,"pubrep_id":"900","doi":"10.1016/j.celrep.2017.04.027","publist_id":"7052","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"oa_version":"Published Version"},{"title":"Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6","status":"public","author":[{"last_name":"Schwarz","first_name":"Jan","full_name":"Schwarz, Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bierbaum, Veronika","id":"3FD04378-F248-11E8-B48F-1D18A9856A87","last_name":"Bierbaum","first_name":"Veronika"},{"full_name":"Vaahtomeri, Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7829-3518","last_name":"Vaahtomeri","first_name":"Kari"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","orcid":"0000-0001-9843-3522","first_name":"Robert"},{"id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus","last_name":"Brown","first_name":"Markus"},{"first_name":"Ingrid","last_name":"De Vries","full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F"},{"first_name":"Anne","orcid":"0000-0003-0666-8928","last_name":"Reversat","full_name":"Reversat, Anne","id":"35B76592-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jack","orcid":"0000-0001-5145-4609","last_name":"Merrin","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tarrant, Teresa","last_name":"Tarrant","first_name":"Teresa"},{"orcid":"0000-0003-4398-476X","last_name":"Bollenbach","first_name":"Tobias","full_name":"Bollenbach, Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","first_name":"Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt"}],"issue":"9","page":"1314 - 1325","quality_controlled":"1","publisher":"Cell Press","publication":"Current Biology","intvolume":"        27","volume":27,"date_created":"2018-12-11T11:47:51Z","date_published":"2017-05-09T00:00:00Z","month":"05","citation":{"chicago":"Schwarz, Jan, Veronika Bierbaum, Kari Vaahtomeri, Robert Hauschild, Markus Brown, Ingrid de Vries, Alexander F Leithner, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” <i>Current Biology</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">https://doi.org/10.1016/j.cub.2017.04.004</a>.","mla":"Schwarz, Jan, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” <i>Current Biology</i>, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:<a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">10.1016/j.cub.2017.04.004</a>.","ista":"Schwarz J, Bierbaum V, Vaahtomeri K, Hauschild R, Brown M, de Vries I, Leithner AF, Reversat A, Merrin J, Tarrant T, Bollenbach MT, Sixt MK. 2017. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. 27(9), 1314–1325.","ama":"Schwarz J, Bierbaum V, Vaahtomeri K, et al. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. <i>Current Biology</i>. 2017;27(9):1314-1325. doi:<a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">10.1016/j.cub.2017.04.004</a>","ieee":"J. Schwarz <i>et al.</i>, “Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6,” <i>Current Biology</i>, vol. 27, no. 9. Cell Press, pp. 1314–1325, 2017.","apa":"Schwarz, J., Bierbaum, V., Vaahtomeri, K., Hauschild, R., Brown, M., de Vries, I., … Sixt, M. K. (2017). Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. <i>Current Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">https://doi.org/10.1016/j.cub.2017.04.004</a>","short":"J. Schwarz, V. Bierbaum, K. Vaahtomeri, R. Hauschild, M. Brown, I. de Vries, A.F. Leithner, A. Reversat, J. Merrin, T. Tarrant, M.T. Bollenbach, M.K. Sixt, Current Biology 27 (2017) 1314–1325."},"day":"09","date_updated":"2023-02-23T12:50:44Z","abstract":[{"text":"Navigation of cells along gradients of guidance cues is a determining step in many developmental and immunological processes. Gradients can either be soluble or immobilized to tissues as demonstrated for the haptotactic migration of dendritic cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate how gradient characteristics govern cellular response patterns, we here introduce an in vitro system allowing to track migratory responses of DCs to precisely controlled immobilized gradients of CCL21. We find that haptotactic sensing depends on the absolute CCL21 concentration and local steepness of the gradient, consistent with a scenario where DC directionality is governed by the signal-to-noise ratio of CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore, we find that CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. These findings suggest that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal guidance in vivo.","lang":"eng"}],"ec_funded":1,"publication_identifier":{"issn":["09609822"]},"_id":"674","language":[{"iso":"eng"}],"publication_status":"published","project":[{"name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734"},{"call_identifier":"FWF","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)"}],"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"NanoFab"}],"publist_id":"7050","doi":"10.1016/j.cub.2017.04.004","oa_version":"None","type":"journal_article","year":"2017","scopus_import":1},{"oa_version":"Published Version","license":"https://creativecommons.org/publicdomain/zero/1.0/","date_published":"2017-08-09T00:00:00Z","date_created":"2018-12-12T12:31:34Z","month":"08","tmp":{"legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)","short":"CC0 (1.0)","image":"/images/cc_0.png"},"has_accepted_license":"1","doi":"10.15479/AT:ISTA:71","file":[{"file_name":"IST-2017-71-v1+1_Synapse_1.avi","date_updated":"2020-07-14T12:47:04Z","checksum":"3d6942d47d0737d064706b5728c4d8c8","date_created":"2018-12-12T13:02:47Z","file_size":236204020,"file_id":"5612","creator":"system","relation":"main_file","access_level":"open_access","content_type":"video/x-msvideo"},{"access_level":"open_access","content_type":"video/x-msvideo","date_created":"2018-12-12T13:02:51Z","file_size":226232496,"file_id":"5613","relation":"main_file","creator":"system","checksum":"4850006c047b0147a9e85b3c2f6f0af4","file_name":"IST-2017-71-v1+2_Synapse_2.avi","date_updated":"2020-07-14T12:47:04Z"}],"day":"09","citation":{"chicago":"Leithner, Alexander F. “Immunological Synapse DC-Tcells.” Institute of Science and Technology Austria, 2017. <a href=\"https://doi.org/10.15479/AT:ISTA:71\">https://doi.org/10.15479/AT:ISTA:71</a>.","ista":"Leithner AF. 2017. Immunological synapse DC-Tcells, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:71\">10.15479/AT:ISTA:71</a>.","ama":"Leithner AF. Immunological synapse DC-Tcells. 2017. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:71\">10.15479/AT:ISTA:71</a>","mla":"Leithner, Alexander F. <i>Immunological Synapse DC-Tcells</i>. Institute of Science and Technology Austria, 2017, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:71\">10.15479/AT:ISTA:71</a>.","short":"A.F. Leithner, (2017).","apa":"Leithner, A. F. (2017). Immunological synapse DC-Tcells. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:71\">https://doi.org/10.15479/AT:ISTA:71</a>","ieee":"A. F. Leithner, “Immunological synapse DC-Tcells.” Institute of Science and Technology Austria, 2017."},"date_updated":"2024-02-21T13:47:00Z","type":"research_data","year":"2017","file_date_updated":"2020-07-14T12:47:04Z","oa":1,"author":[{"last_name":"Leithner","orcid":"0000-0002-1073-744X","first_name":"Alexander F","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","title":"Immunological synapse DC-Tcells","abstract":[{"lang":"eng","text":"Immunological synapse DC-Tcells"}],"status":"public","publisher":"Institute of Science and Technology Austria","keyword":["Immunological synapse"],"department":[{"_id":"MiSi"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","datarep_id":"71","ddc":["570"],"_id":"5567"},{"date_published":"2016-10-24T00:00:00Z","date_created":"2018-12-11T11:51:21Z","month":"10","has_accepted_license":"1","volume":18,"article_type":"original","file":[{"access_level":"open_access","content_type":"application/pdf","date_created":"2020-05-14T16:33:46Z","relation":"main_file","file_id":"7844","creator":"dernst","file_size":4433280,"checksum":"e1411cb7c99a2d9089c178a6abef25e7","file_name":"2018_NatureCell_Leithner.pdf","date_updated":"2020-07-14T12:44:43Z"}],"citation":{"ista":"Leithner AF, Eichner A, Müller J, Reversat A, Brown M, Schwarz J, Merrin J, De Gorter D, Schur FK, Bayerl J, de Vries I, Wieser S, Hauschild R, Lai F, Moser M, Kerjaschki D, Rottner K, Small V, Stradal T, Sixt MK. 2016. Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. 18, 1253–1259.","ama":"Leithner AF, Eichner A, Müller J, et al. Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. <i>Nature Cell Biology</i>. 2016;18:1253-1259. doi:<a href=\"https://doi.org/10.1038/ncb3426\">10.1038/ncb3426</a>","mla":"Leithner, Alexander F., et al. “Diversified Actin Protrusions Promote Environmental Exploration but Are Dispensable for Locomotion of Leukocytes.” <i>Nature Cell Biology</i>, vol. 18, Nature Publishing Group, 2016, pp. 1253–59, doi:<a href=\"https://doi.org/10.1038/ncb3426\">10.1038/ncb3426</a>.","chicago":"Leithner, Alexander F, Alexander Eichner, Jan Müller, Anne Reversat, Markus Brown, Jan Schwarz, Jack Merrin, et al. “Diversified Actin Protrusions Promote Environmental Exploration but Are Dispensable for Locomotion of Leukocytes.” <i>Nature Cell Biology</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/ncb3426\">https://doi.org/10.1038/ncb3426</a>.","apa":"Leithner, A. F., Eichner, A., Müller, J., Reversat, A., Brown, M., Schwarz, J., … Sixt, M. K. (2016). Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. <i>Nature Cell Biology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ncb3426\">https://doi.org/10.1038/ncb3426</a>","short":"A.F. Leithner, A. Eichner, J. Müller, A. Reversat, M. Brown, J. Schwarz, J. Merrin, D. De Gorter, F.K. Schur, J. Bayerl, I. de Vries, S. Wieser, R. Hauschild, F. Lai, M. Moser, D. Kerjaschki, K. Rottner, V. Small, T. Stradal, M.K. Sixt, Nature Cell Biology 18 (2016) 1253–1259.","ieee":"A. F. Leithner <i>et al.</i>, “Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes,” <i>Nature Cell Biology</i>, vol. 18. Nature Publishing Group, pp. 1253–1259, 2016."},"day":"24","date_updated":"2024-03-25T23:30:09Z","related_material":{"record":[{"id":"323","relation":"dissertation_contains","status":"public"}]},"oa":1,"author":[{"last_name":"Leithner","orcid":"0000-0002-1073-744X","first_name":"Alexander F","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"id":"4DFA52AE-F248-11E8-B48F-1D18A9856A87","full_name":"Eichner, Alexander","first_name":"Alexander","last_name":"Eichner"},{"full_name":"Müller, Jan","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D","first_name":"Jan","last_name":"Müller"},{"id":"35B76592-F248-11E8-B48F-1D18A9856A87","full_name":"Reversat, Anne","first_name":"Anne","last_name":"Reversat","orcid":"0000-0003-0666-8928"},{"last_name":"Brown","first_name":"Markus","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Schwarz","first_name":"Jan","full_name":"Schwarz, Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"id":"4515C308-F248-11E8-B48F-1D18A9856A87","full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","last_name":"Merrin","first_name":"Jack"},{"first_name":"David","last_name":"De Gorter","full_name":"De Gorter, David"},{"first_name":"Florian","last_name":"Schur","orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian"},{"first_name":"Jonathan","last_name":"Bayerl","full_name":"Bayerl, Jonathan"},{"last_name":"De Vries","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid"},{"last_name":"Wieser","orcid":"0000-0002-2670-2217","first_name":"Stefan","full_name":"Wieser, Stefan","id":"355AA5A0-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hauschild","orcid":"0000-0001-9843-3522","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert"},{"full_name":"Lai, Frank","last_name":"Lai","first_name":"Frank"},{"full_name":"Moser, Markus","first_name":"Markus","last_name":"Moser"},{"full_name":"Kerjaschki, Dontscho","first_name":"Dontscho","last_name":"Kerjaschki"},{"full_name":"Rottner, Klemens","first_name":"Klemens","last_name":"Rottner"},{"full_name":"Small, Victor","last_name":"Small","first_name":"Victor"},{"full_name":"Stradal, Theresia","first_name":"Theresia","last_name":"Stradal"},{"orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"title":"Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes","status":"public","publisher":"Nature Publishing Group","page":"1253 - 1259","quality_controlled":"1","intvolume":"        18","publication":"Nature Cell Biology","acknowledged_ssus":[{"_id":"SSU"}],"oa_version":"Submitted Version","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","short":"CC BY-NC-SA (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png"},"publist_id":"5949","doi":"10.1038/ncb3426","scopus_import":1,"year":"2016","type":"journal_article","file_date_updated":"2020-07-14T12:44:43Z","article_processing_charge":"No","acknowledgement":"This work was supported by the German Research Foundation (DFG) Priority Program SP 1464 to T.E.B.S. and M.S., and European Research Council (ERC GA 281556) and Human Frontiers Program grants to M.S.\r\nService Units of IST Austria for excellent technical support.","abstract":[{"text":"Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion.","lang":"eng"}],"ec_funded":1,"project":[{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","call_identifier":"FP7"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"ddc":["570"],"publication_status":"published","language":[{"iso":"eng"}],"_id":"1321"}]