[{"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"        14","abstract":[{"text":"Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient data indicate that the lymphatic capillary density directly correlates with functional output, i.e., tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms ensuring efficient tissue coverage remain poorly understood. Here, we use the mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing, genetic perturbations, whole-organ reconstructions and theoretical modeling to show that the dermal lymphatic capillaries tile space in an optimal, space-filling manner. This coverage is achieved by two complementary mechanisms: initial tissue invasion provides a non-optimal global scaffold via self-organized branching morphogenesis, while VEGF-C dependent side-branching from existing capillaries rapidly optimizes local coverage by directionally targeting low-density regions. With these two ingredients, we show that a minimal biophysical model can reproduce quantitatively whole-network reconstructions, across development and perturbations. Our results show that lymphatic capillary networks can exploit local self-organizing mechanisms to achieve tissue-scale optimization.","lang":"eng"}],"has_accepted_license":"1","publication_status":"published","publication_identifier":{"eissn":["2041-1723"]},"file_date_updated":"2023-10-03T07:46:36Z","title":"Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks","oa_version":"Published Version","author":[{"last_name":"Ucar","id":"50B2A802-6007-11E9-A42B-EB23E6697425","full_name":"Ucar, Mehmet C","first_name":"Mehmet C","orcid":"0000-0003-0506-4217"},{"first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B","last_name":"Hannezo"},{"first_name":"Emmi","full_name":"Tiilikainen, Emmi","last_name":"Tiilikainen"},{"full_name":"Liaqat, Inam","last_name":"Liaqat","first_name":"Inam"},{"full_name":"Jakobsson, Emma","last_name":"Jakobsson","first_name":"Emma"},{"full_name":"Nurmi, Harri","last_name":"Nurmi","first_name":"Harri"},{"orcid":"0000-0001-7829-3518","first_name":"Kari","full_name":"Vaahtomeri, Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","last_name":"Vaahtomeri"}],"scopus_import":"1","day":"21","article_type":"original","date_created":"2023-10-01T22:01:13Z","volume":14,"language":[{"iso":"eng"}],"oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"short":"M.C. Ucar, E.B. Hannezo, E. Tiilikainen, I. Liaqat, E. Jakobsson, H. Nurmi, K. Vaahtomeri, Nature Communications 14 (2023).","ieee":"M. C. Ucar <i>et al.</i>, “Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks,” <i>Nature Communications</i>, vol. 14. Springer Nature, 2023.","ama":"Ucar MC, Hannezo EB, Tiilikainen E, et al. Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. <i>Nature Communications</i>. 2023;14. doi:<a href=\"https://doi.org/10.1038/s41467-023-41456-7\">10.1038/s41467-023-41456-7</a>","mla":"Ucar, Mehmet C., et al. “Self-Organized and Directed Branching Results in Optimal Coverage in Developing Dermal Lymphatic Networks.” <i>Nature Communications</i>, vol. 14, 5878, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41467-023-41456-7\">10.1038/s41467-023-41456-7</a>.","apa":"Ucar, M. C., Hannezo, E. B., Tiilikainen, E., Liaqat, I., Jakobsson, E., Nurmi, H., &#38; Vaahtomeri, K. (2023). Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-023-41456-7\">https://doi.org/10.1038/s41467-023-41456-7</a>","chicago":"Ucar, Mehmet C, Edouard B Hannezo, Emmi Tiilikainen, Inam Liaqat, Emma Jakobsson, Harri Nurmi, and Kari Vaahtomeri. “Self-Organized and Directed Branching Results in Optimal Coverage in Developing Dermal Lymphatic Networks.” <i>Nature Communications</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41467-023-41456-7\">https://doi.org/10.1038/s41467-023-41456-7</a>.","ista":"Ucar MC, Hannezo EB, Tiilikainen E, Liaqat I, Jakobsson E, Nurmi H, Vaahtomeri K. 2023. Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. Nature Communications. 14, 5878."},"month":"09","article_number":"5878","file":[{"checksum":"4fe5423403f2531753bcd9e0fea48e05","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_name":"2023_NatureComm_Ucar.pdf","file_id":"14384","creator":"dernst","date_updated":"2023-10-03T07:46:36Z","file_size":8143264,"date_created":"2023-10-03T07:46:36Z"}],"department":[{"_id":"EdHa"}],"ddc":["570"],"quality_controlled":"1","publisher":"Springer Nature","doi":"10.1038/s41467-023-41456-7","article_processing_charge":"Yes","type":"journal_article","date_updated":"2023-12-13T12:31:05Z","_id":"14378","project":[{"grant_number":"851288","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E"},{"call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"publication":"Nature Communications","status":"public","date_published":"2023-09-21T00:00:00Z","acknowledgement":"We thank Dr. Kari Alitalo (University of Helsinki and Wihuri Research Institute) for critical reading of the manuscript, providing Vegfc+/− and Clp24ΔEC mouse strains and for hosting K.V.’s Academy of Finland postdoctoral researcher period (2015–2018). We thank Dr. Sara Wickström (University of Helsinki and Wihuri Research Institute) for providing Sox9:Egfp mouse\r\nstrain and the discussions. We thank Maija Atuegwu and Tapio Tainola for technical assistance. This work received funding from the Academy of Finland (K.V., 315710), Sigrid Juselius Foundation (K.V.), University of Helsinki (K.V.), Wihuri Research Institute (K.V.), the ERC under the European Union’s Horizon 2020 research and innovation program (grant agreement\r\nNo. 851288 to E.H.) and under the Marie Skłodowska-Curie grant agreement No. 754411 (to M.C.U.). Part of the work was carried out with the support of HiLIFE Laboratory Animal Centre Core Facility, University of Helsinki, Finland. Imaging was performed at the Biomedicum Imaging Unit, Helsinki University, Helsinki, Finland, with the support of Biocenter Finland. The AAVpreparations were produced at the Helsinki Virus (HelVi) Core.","pmid":1,"ec_funded":1,"external_id":{"pmid":["37735168"],"isi":["001075884500007"]},"year":"2023","isi":1},{"has_accepted_license":"1","intvolume":"        12","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"text":"Gradients of chemokines and growth factors guide migrating cells and morphogenetic processes. Migration of antigen-presenting dendritic cells from the interstitium into the lymphatic system is dependent on chemokine CCL21, which is secreted by endothelial cells of the lymphatic capillary, binds heparan sulfates and forms gradients decaying into the interstitium. Despite the importance of CCL21 gradients, and chemokine gradients in general, the mechanisms of gradient formation are unclear. Studies on fibroblast growth factors have shown that limited diffusion is crucial for gradient formation. Here, we used the mouse dermis as a model tissue to address the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels at the lymphatic capillaries and did neither affect interstitial CCL21 gradient shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan sulfates at the level of the lymphatic endothelium are dispensable for the formation of a functional CCL21 gradient.","lang":"eng"}],"file_date_updated":"2021-03-22T12:08:26Z","publication_status":"published","publication_identifier":{"eissn":["1664-3224"]},"scopus_import":"1","day":"25","author":[{"last_name":"Vaahtomeri","id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari","first_name":"Kari","orcid":"0000-0001-7829-3518"},{"last_name":"Moussion","id":"3356F664-F248-11E8-B48F-1D18A9856A87","full_name":"Moussion, Christine","first_name":"Christine"},{"orcid":"0000-0001-9843-3522","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","last_name":"Hauschild"},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt"}],"oa_version":"Published Version","title":"Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium","volume":12,"date_created":"2021-03-21T23:01:20Z","article_type":"original","oa":1,"language":[{"iso":"eng"}],"citation":{"ama":"Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. <i>Frontiers in Immunology</i>. 2021;12. doi:<a href=\"https://doi.org/10.3389/fimmu.2021.630002\">10.3389/fimmu.2021.630002</a>","ieee":"K. Vaahtomeri, C. Moussion, R. Hauschild, and M. K. Sixt, “Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium,” <i>Frontiers in Immunology</i>, vol. 12. Frontiers, 2021.","short":"K. Vaahtomeri, C. Moussion, R. Hauschild, M.K. Sixt, Frontiers in Immunology 12 (2021).","ista":"Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. 2021. Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Frontiers in Immunology. 12, 630002.","chicago":"Vaahtomeri, Kari, Christine Moussion, Robert Hauschild, and Michael K Sixt. “Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.” <i>Frontiers in Immunology</i>. Frontiers, 2021. <a href=\"https://doi.org/10.3389/fimmu.2021.630002\">https://doi.org/10.3389/fimmu.2021.630002</a>.","apa":"Vaahtomeri, K., Moussion, C., Hauschild, R., &#38; Sixt, M. K. (2021). Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. <i>Frontiers in Immunology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fimmu.2021.630002\">https://doi.org/10.3389/fimmu.2021.630002</a>","mla":"Vaahtomeri, Kari, et al. “Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.” <i>Frontiers in Immunology</i>, vol. 12, 630002, Frontiers, 2021, doi:<a href=\"https://doi.org/10.3389/fimmu.2021.630002\">10.3389/fimmu.2021.630002</a>."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"02","department":[{"_id":"MiSi"},{"_id":"Bio"}],"article_number":"630002","file":[{"date_updated":"2021-03-22T12:08:26Z","creator":"dernst","date_created":"2021-03-22T12:08:26Z","file_size":3740146,"file_id":"9277","content_type":"application/pdf","access_level":"open_access","file_name":"2021_FrontiersImmumo_Vaahtomeri.pdf","success":1,"checksum":"663f5a48375e42afa4bfef58d42ec186","relation":"main_file"}],"ddc":["570"],"quality_controlled":"1","article_processing_charge":"No","doi":"10.3389/fimmu.2021.630002","publisher":"Frontiers","_id":"9259","date_updated":"2023-08-07T14:18:26Z","type":"journal_article","status":"public","publication":"Frontiers in Immunology","project":[{"call_identifier":"H2020","grant_number":"724373","name":"Cellular navigation along spatial gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"Y 564-B12"}],"ec_funded":1,"pmid":1,"acknowledgement":"This work was supported by Sigrid Juselius fellowship (KV), University of Helsinki 3-year research grant (KV), Academy of Finland Research fellow funding (315710, to KV), the European Research Council (ERC CoG 724373 to MS), and by the Austrian Science foundation (FWF) (Y564-B12 START award to MS).\r\nTaija Mäkinen is acknowledged for providing Prox1CreERT2 transgenic mice and Yu Yamaguchi for providing the conditional Ext1 mouse strain.","date_published":"2021-02-25T00:00:00Z","isi":1,"year":"2021","external_id":{"isi":["000627134400001"],"pmid":["33717158"]}},{"abstract":[{"lang":"eng","text":"Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified &gt; 1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments."}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"       217","has_accepted_license":"1","file_date_updated":"2020-07-14T12:45:45Z","publication_status":"published","oa_version":"Published Version","title":"Lymphatic exosomes promote dendritic cell migration along guidance cues","scopus_import":"1","day":"12","author":[{"first_name":"Markus","last_name":"Brown","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Johnson, Louise","last_name":"Johnson","first_name":"Louise"},{"first_name":"Dario","full_name":"Leone, Dario","last_name":"Leone"},{"first_name":"Peter","last_name":"Májek","full_name":"Májek, Peter"},{"last_name":"Vaahtomeri","full_name":"Vaahtomeri, Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7829-3518","first_name":"Kari"},{"last_name":"Senfter","full_name":"Senfter, Daniel","first_name":"Daniel"},{"last_name":"Bukosza","full_name":"Bukosza, Nora","first_name":"Nora"},{"last_name":"Schachner","full_name":"Schachner, Helga","first_name":"Helga"},{"first_name":"Gabriele","last_name":"Asfour","full_name":"Asfour, Gabriele"},{"last_name":"Langer","full_name":"Langer, Brigitte","first_name":"Brigitte"},{"first_name":"Robert","orcid":"0000-0001-9843-3522","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert"},{"last_name":"Parapatics","full_name":"Parapatics, Katja","first_name":"Katja"},{"first_name":"Young","full_name":"Hong, Young","last_name":"Hong"},{"first_name":"Keiryn","last_name":"Bennett","full_name":"Bennett, Keiryn"},{"last_name":"Kain","full_name":"Kain, Renate","first_name":"Renate"},{"first_name":"Michael","full_name":"Detmar, Michael","last_name":"Detmar"},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt"},{"full_name":"Jackson, David","last_name":"Jackson","first_name":"David"},{"last_name":"Kerjaschki","full_name":"Kerjaschki, Dontscho","first_name":"Dontscho"}],"date_created":"2018-12-11T11:45:33Z","volume":217,"language":[{"iso":"eng"}],"oa":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Brown, Markus, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration along Guidance Cues.” <i>Journal of Cell Biology</i>, vol. 217, no. 6, Rockefeller University Press, 2018, pp. 2205–21, doi:<a href=\"https://doi.org/10.1083/jcb.201612051\">10.1083/jcb.201612051</a>.","apa":"Brown, M., Johnson, L., Leone, D., Májek, P., Vaahtomeri, K., Senfter, D., … Kerjaschki, D. (2018). Lymphatic exosomes promote dendritic cell migration along guidance cues. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.201612051\">https://doi.org/10.1083/jcb.201612051</a>","chicago":"Brown, Markus, Louise Johnson, Dario Leone, Peter Májek, Kari Vaahtomeri, Daniel Senfter, Nora Bukosza, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration along Guidance Cues.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2018. <a href=\"https://doi.org/10.1083/jcb.201612051\">https://doi.org/10.1083/jcb.201612051</a>.","ista":"Brown M, Johnson L, Leone D, Májek P, Vaahtomeri K, Senfter D, Bukosza N, Schachner H, Asfour G, Langer B, Hauschild R, Parapatics K, Hong Y, Bennett K, Kain R, Detmar M, Sixt MK, Jackson D, Kerjaschki D. 2018. Lymphatic exosomes promote dendritic cell migration along guidance cues. Journal of Cell Biology. 217(6), 2205–2221.","short":"M. Brown, L. Johnson, D. Leone, P. Májek, K. Vaahtomeri, D. Senfter, N. Bukosza, H. Schachner, G. Asfour, B. Langer, R. Hauschild, K. Parapatics, Y. Hong, K. Bennett, R. Kain, M. Detmar, M.K. Sixt, D. Jackson, D. Kerjaschki, Journal of Cell Biology 217 (2018) 2205–2221.","ieee":"M. Brown <i>et al.</i>, “Lymphatic exosomes promote dendritic cell migration along guidance cues,” <i>Journal of Cell Biology</i>, vol. 217, no. 6. Rockefeller University Press, pp. 2205–2221, 2018.","ama":"Brown M, Johnson L, Leone D, et al. Lymphatic exosomes promote dendritic cell migration along guidance cues. <i>Journal of Cell Biology</i>. 2018;217(6):2205-2221. doi:<a href=\"https://doi.org/10.1083/jcb.201612051\">10.1083/jcb.201612051</a>"},"issue":"6","month":"04","file":[{"file_id":"5704","date_updated":"2020-07-14T12:45:45Z","creator":"dernst","date_created":"2018-12-17T12:50:07Z","file_size":2252043,"checksum":"9c7eba51a35c62da8c13f98120b64df4","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2018_JournalCellBiology_Brown.pdf"}],"department":[{"_id":"MiSi"},{"_id":"Bio"}],"ddc":["570"],"page":"2205 - 2221","quality_controlled":"1","publisher":"Rockefeller University Press","article_processing_charge":"No","doi":"10.1083/jcb.201612051","type":"journal_article","_id":"275","date_updated":"2023-09-13T08:51:29Z","publication":"Journal of Cell Biology","status":"public","project":[{"_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12","call_identifier":"FWF"},{"call_identifier":"FP7","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","_id":"25A603A2-B435-11E9-9278-68D0E5697425"}],"date_published":"2018-04-12T00:00:00Z","acknowledgement":"M. Brown was supported by the Cell Communication in Health and Disease Graduate Study Program of the Austrian Science Fund and Medizinische Universität Wien, M. Sixt by the European Research Council (ERC GA 281556) and an Austrian Science Fund START award, K.L. Bennett by the Austrian Academy of Sciences, D.G. Jackson and L.A. Johnson by Unit Funding (MC_UU_12010/2) and project grants from the Medical Research Council (G1100134 and MR/L008610/1), and M. Detmar by the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung and Advanced European Research Council grant LYVICAM. K. Vaahtomeri was supported by an Academy of Finland postdoctoral research grant (287853). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668036 (RELENT).","ec_funded":1,"pmid":1,"external_id":{"isi":["000438077800026"],"pmid":["29650776"]},"year":"2018","isi":1,"publist_id":"7627"},{"date_created":"2018-12-11T11:47:50Z","volume":19,"oa_version":"Published Version","title":"Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia","day":"02","scopus_import":1,"author":[{"first_name":"Kari","orcid":"0000-0001-7829-3518","full_name":"Vaahtomeri, Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","last_name":"Vaahtomeri"},{"last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus","first_name":"Markus"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid","last_name":"De Vries","first_name":"Ingrid"},{"first_name":"Alexander F","last_name":"Leithner","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Mehling, Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87","last_name":"Mehling","first_name":"Matthias","orcid":"0000-0001-8599-1226"},{"first_name":"Walter","orcid":"0000-0001-9735-5315","last_name":"Kaufmann","full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179"}],"file_date_updated":"2020-07-14T12:47:38Z","publication_identifier":{"issn":["22111247"]},"publication_status":"published","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"intvolume":"        19","abstract":[{"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.","lang":"eng"}],"has_accepted_license":"1","file":[{"checksum":"8fdddaab1f1d76a6ec9ca94dcb6b07a2","relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_name":"IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf","file_id":"5109","creator":"system","date_updated":"2020-07-14T12:47:38Z","date_created":"2018-12-12T10:14:54Z","file_size":2248814}],"department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}],"month":"05","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"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>","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.","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>.","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.","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>"},"issue":"5","language":[{"iso":"eng"}],"pubrep_id":"900","oa":1,"type":"journal_article","_id":"672","date_updated":"2023-02-23T12:50:09Z","publisher":"Cell Press","article_processing_charge":"Yes","doi":"10.1016/j.celrep.2017.04.027","quality_controlled":"1","ddc":["570"],"page":"902 - 909","publist_id":"7052","year":"2017","date_published":"2017-05-02T00:00:00Z","ec_funded":1,"status":"public","publication":"Cell Reports","project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"},{"_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12","call_identifier":"FWF"}]},{"year":"2017","publist_id":"7050","publication":"Current Biology","status":"public","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"Y 564-B12","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"ec_funded":1,"date_published":"2017-05-09T00:00:00Z","doi":"10.1016/j.cub.2017.04.004","publisher":"Cell Press","_id":"674","date_updated":"2023-02-23T12:50:44Z","type":"journal_article","page":"1314 - 1325","quality_controlled":"1","month":"05","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"NanoFab"}],"language":[{"iso":"eng"}],"citation":{"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>.","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>","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.","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>.","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.","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.","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>"},"issue":"9","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","day":"09","scopus_import":1,"author":[{"first_name":"Jan","last_name":"Schwarz","full_name":"Schwarz, Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bierbaum","full_name":"Bierbaum, Veronika","id":"3FD04378-F248-11E8-B48F-1D18A9856A87","first_name":"Veronika"},{"last_name":"Vaahtomeri","id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari","first_name":"Kari","orcid":"0000-0001-7829-3518"},{"last_name":"Hauschild","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","first_name":"Robert"},{"first_name":"Markus","last_name":"Brown","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"De Vries","full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F"},{"orcid":"0000-0003-0666-8928","first_name":"Anne","full_name":"Reversat, Anne","id":"35B76592-F248-11E8-B48F-1D18A9856A87","last_name":"Reversat"},{"last_name":"Merrin","id":"4515C308-F248-11E8-B48F-1D18A9856A87","full_name":"Merrin, Jack","first_name":"Jack","orcid":"0000-0001-5145-4609"},{"first_name":"Teresa","full_name":"Tarrant, Teresa","last_name":"Tarrant"},{"last_name":"Bollenbach","full_name":"Bollenbach, Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","first_name":"Tobias"},{"last_name":"Sixt","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179"}],"title":"Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6","oa_version":"None","volume":27,"date_created":"2018-12-11T11:47:51Z","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"}],"intvolume":"        27","publication_identifier":{"issn":["09609822"]},"publication_status":"published"},{"citation":{"chicago":"Martins, Rui, Julia Maier, Anna Gorki, Kilian Huber, Omar Sharif, Philipp Starkl, Simona Saluzzo, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions.” <i>Nature Immunology</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/ni.3590\">https://doi.org/10.1038/ni.3590</a>.","ista":"Martins R, Maier J, Gorki A, Huber K, Sharif O, Starkl P, Saluzzo S, Quattrone F, Gawish R, Lakovits K, Aichinger M, Radic Sarikas B, Lardeau C, Hladik A, Korosec A, Brown M, Vaahtomeri K, Duggan M, Kerjaschki D, Esterbauer H, Colinge J, Eisenbarth S, Decker T, Bennett K, Kubicek S, Sixt MK, Superti Furga G, Knapp S. 2016. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nature Immunology. 17(12), 1361–1372.","mla":"Martins, Rui, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions.” <i>Nature Immunology</i>, vol. 17, no. 12, Nature Publishing Group, 2016, pp. 1361–72, doi:<a href=\"https://doi.org/10.1038/ni.3590\">10.1038/ni.3590</a>.","apa":"Martins, R., Maier, J., Gorki, A., Huber, K., Sharif, O., Starkl, P., … Knapp, S. (2016). Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. <i>Nature Immunology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ni.3590\">https://doi.org/10.1038/ni.3590</a>","ama":"Martins R, Maier J, Gorki A, et al. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. <i>Nature Immunology</i>. 2016;17(12):1361-1372. doi:<a href=\"https://doi.org/10.1038/ni.3590\">10.1038/ni.3590</a>","short":"R. Martins, J. Maier, A. Gorki, K. Huber, O. Sharif, P. Starkl, S. Saluzzo, F. Quattrone, R. Gawish, K. Lakovits, M. Aichinger, B. Radic Sarikas, C. Lardeau, A. Hladik, A. Korosec, M. Brown, K. Vaahtomeri, M. Duggan, D. Kerjaschki, H. Esterbauer, J. Colinge, S. Eisenbarth, T. Decker, K. Bennett, S. Kubicek, M.K. Sixt, G. Superti Furga, S. Knapp, Nature Immunology 17 (2016) 1361–1372.","ieee":"R. Martins <i>et al.</i>, “Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions,” <i>Nature Immunology</i>, vol. 17, no. 12. Nature Publishing Group, pp. 1361–1372, 2016."},"issue":"12","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"MiSi"},{"_id":"PeJo"}],"month":"12","publication_status":"published","intvolume":"        17","abstract":[{"text":"Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach revealed that quinine effectively prevented heme effects on the cytoskeleton, restored phagocytosis and improved survival in sepsis. These mechanistic insights provide potential therapeutic targets for patients with sepsis or hemolytic disorders.","lang":"eng"}],"volume":17,"date_created":"2018-12-11T11:50:22Z","day":"01","scopus_import":1,"author":[{"first_name":"Rui","last_name":"Martins","full_name":"Martins, Rui"},{"first_name":"Julia","full_name":"Maier, Julia","last_name":"Maier"},{"first_name":"Anna","full_name":"Gorki, Anna","last_name":"Gorki"},{"last_name":"Huber","full_name":"Huber, Kilian","first_name":"Kilian"},{"first_name":"Omar","last_name":"Sharif","full_name":"Sharif, Omar"},{"first_name":"Philipp","last_name":"Starkl","full_name":"Starkl, Philipp"},{"first_name":"Simona","last_name":"Saluzzo","full_name":"Saluzzo, Simona"},{"full_name":"Quattrone, Federica","last_name":"Quattrone","first_name":"Federica"},{"first_name":"Riem","last_name":"Gawish","full_name":"Gawish, Riem"},{"first_name":"Karin","last_name":"Lakovits","full_name":"Lakovits, Karin"},{"last_name":"Aichinger","full_name":"Aichinger, Michael","first_name":"Michael"},{"first_name":"Branka","full_name":"Radic Sarikas, Branka","last_name":"Radic Sarikas"},{"full_name":"Lardeau, Charles","last_name":"Lardeau","first_name":"Charles"},{"first_name":"Anastasiya","last_name":"Hladik","full_name":"Hladik, Anastasiya"},{"full_name":"Korosec, Ana","last_name":"Korosec","first_name":"Ana"},{"first_name":"Markus","last_name":"Brown","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Vaahtomeri","full_name":"Vaahtomeri, Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7829-3518","first_name":"Kari"},{"last_name":"Duggan","full_name":"Duggan, Michelle","id":"2EDEA62C-F248-11E8-B48F-1D18A9856A87","first_name":"Michelle"},{"first_name":"Dontscho","full_name":"Kerjaschki, Dontscho","last_name":"Kerjaschki"},{"first_name":"Harald","last_name":"Esterbauer","full_name":"Esterbauer, Harald"},{"last_name":"Colinge","full_name":"Colinge, Jacques","first_name":"Jacques"},{"first_name":"Stephanie","full_name":"Eisenbarth, Stephanie","last_name":"Eisenbarth"},{"first_name":"Thomas","last_name":"Decker","full_name":"Decker, Thomas"},{"first_name":"Keiryn","last_name":"Bennett","full_name":"Bennett, Keiryn"},{"full_name":"Kubicek, Stefan","last_name":"Kubicek","first_name":"Stefan"},{"last_name":"Sixt","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K"},{"first_name":"Giulio","last_name":"Superti Furga","full_name":"Superti Furga, Giulio"},{"first_name":"Sylvia","last_name":"Knapp","full_name":"Knapp, Sylvia"}],"title":"Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions","oa_version":"Submitted Version","acknowledgement":"Y. Fukui (Medical Institute of Bioregulation, Kyushu University) and J. Stein (Theodor Kocher Institute, University of Bern) are acknowledged for providing the DOCK8 deficient bone marrow. and H. Häcker (St. Judes Children's Research Hospital) for providing the ERHBD-HoxB8-encoding retroviral construct. pSpCas9(BB)-2a-Puro (PX459) was a gift from F. Zhang (Massachusetts Institute of Technology) (Addgene plasmid # 48139) and pGRG36 was a gift from N. Craig (Johns Hopkins University School of Medicine) (Addgene plasmid # 16666). LifeAct-GFP-encoding retrovirus was kindly provided by A. Leithner (Institute of Science and Technology Austria). pSIM8 and TKC E. coli were gifts from D.L. Court (Center for Cancer Research, National Cancer Institute). We acknowledge M. Gröger and S. Rauscher for excellent technical support (Core imaging facility, Medical University of Vienna). We thank D.P. Barlow and L.R. Cheever for critical reading of the manuscript. This work was supported by the Austrian Academy of Sciences, the Science Fund of the Austrian National Bank (14107) and the Austrian Science Fund FWF (I1620-B22) in the Infect-ERA framework (to S.Knapp).","date_published":"2016-12-01T00:00:00Z","status":"public","publication":"Nature Immunology","publist_id":"6216","year":"2016","main_file_link":[{"open_access":"1","url":"https://ora.ox.ac.uk/objects/uuid:f53a464e-1e5b-4f08-a7d8-b6749b852b9d"}],"quality_controlled":"1","page":"1361 - 1372","_id":"1142","date_updated":"2021-01-12T06:48:36Z","type":"journal_article","doi":"10.1038/ni.3590","publisher":"Nature Publishing Group"},{"quality_controlled":"1","page":"1723 - 1734","ddc":["570"],"date_updated":"2021-01-12T06:51:07Z","_id":"1490","type":"journal_article","doi":"10.1016/j.celrep.2016.01.048","publisher":"Cell Press","date_published":"2016-02-23T00:00:00Z","publication":"Cell Reports","status":"public","publist_id":"5697","year":"2016","publication_status":"published","file_date_updated":"2020-07-14T12:44:58Z","has_accepted_license":"1","intvolume":"        14","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"abstract":[{"text":"To induce adaptive immunity, dendritic cells (DCs) migrate through afferent lymphatic vessels (LVs) to draining lymph nodes (dLNs). This process occurs in several consecutive steps. Upon entry into lymphatic capillaries, DCs first actively crawl into downstream collecting vessels. From there, they are next passively and rapidly transported to the dLN by lymph flow. Here, we describe a role for the chemokine CCL21 in intralymphatic DC crawling. Performing time-lapse imaging in murine skin, we found that blockade of CCL21-but not the absence of lymph flow-completely abolished DC migration from capillaries toward collecting vessels and reduced the ability of intralymphatic DCs to emigrate from skin. Moreover, we found that in vitro low laminar flow established a CCL21 gradient along lymphatic endothelial monolayers, thereby inducing downstream-directed DC migration. These findings reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through the formation of a flow-induced gradient.","lang":"eng"}],"volume":14,"date_created":"2018-12-11T11:52:19Z","author":[{"last_name":"Russo","full_name":"Russo, Erica","first_name":"Erica"},{"last_name":"Teijeira","full_name":"Teijeira, Alvaro","first_name":"Alvaro"},{"orcid":"0000-0001-7829-3518","first_name":"Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari","last_name":"Vaahtomeri"},{"last_name":"Willrodt","full_name":"Willrodt, Ann","first_name":"Ann"},{"last_name":"Bloch","full_name":"Bloch, Joël","first_name":"Joël"},{"first_name":"Maximilian","full_name":"Nitschké, Maximilian","last_name":"Nitschké"},{"full_name":"Santambrogio, Laura","last_name":"Santambrogio","first_name":"Laura"},{"full_name":"Kerjaschki, Dontscho","last_name":"Kerjaschki","first_name":"Dontscho"},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"},{"first_name":"Cornelia","full_name":"Halin, Cornelia","last_name":"Halin"}],"scopus_import":1,"day":"23","oa_version":"Published Version","title":"Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels","issue":"7","citation":{"ista":"Russo E, Teijeira A, Vaahtomeri K, Willrodt A, Bloch J, Nitschké M, Santambrogio L, Kerjaschki D, Sixt MK, Halin C. 2016. Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels. Cell Reports. 14(7), 1723–1734.","chicago":"Russo, Erica, Alvaro Teijeira, Kari Vaahtomeri, Ann Willrodt, Joël Bloch, Maximilian Nitschké, Laura Santambrogio, Dontscho Kerjaschki, Michael K Sixt, and Cornelia Halin. “Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels.” <i>Cell Reports</i>. Cell Press, 2016. <a href=\"https://doi.org/10.1016/j.celrep.2016.01.048\">https://doi.org/10.1016/j.celrep.2016.01.048</a>.","apa":"Russo, E., Teijeira, A., Vaahtomeri, K., Willrodt, A., Bloch, J., Nitschké, M., … Halin, C. (2016). Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2016.01.048\">https://doi.org/10.1016/j.celrep.2016.01.048</a>","mla":"Russo, Erica, et al. “Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels.” <i>Cell Reports</i>, vol. 14, no. 7, Cell Press, 2016, pp. 1723–34, doi:<a href=\"https://doi.org/10.1016/j.celrep.2016.01.048\">10.1016/j.celrep.2016.01.048</a>.","ama":"Russo E, Teijeira A, Vaahtomeri K, et al. Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels. <i>Cell Reports</i>. 2016;14(7):1723-1734. doi:<a href=\"https://doi.org/10.1016/j.celrep.2016.01.048\">10.1016/j.celrep.2016.01.048</a>","ieee":"E. Russo <i>et al.</i>, “Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels,” <i>Cell Reports</i>, vol. 14, no. 7. Cell Press, pp. 1723–1734, 2016.","short":"E. Russo, A. Teijeira, K. Vaahtomeri, A. Willrodt, J. Bloch, M. Nitschké, L. Santambrogio, D. Kerjaschki, M.K. Sixt, C. Halin, Cell Reports 14 (2016) 1723–1734."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa":1,"language":[{"iso":"eng"}],"pubrep_id":"515","department":[{"_id":"MiSi"}],"file":[{"date_updated":"2020-07-14T12:44:58Z","creator":"system","date_created":"2018-12-12T10:12:30Z","file_size":5489897,"file_id":"4948","content_type":"application/pdf","access_level":"open_access","file_name":"IST-2016-515-v1+1_1-s2.0-S2211124716300262-main.pdf","checksum":"c98c1151d5f1e5ce1643a83d8d7f3c29","relation":"main_file"}],"month":"02"},{"date_created":"2018-12-11T11:54:30Z","type":"journal_article","article_type":"letter_note","_id":"1877","volume":514,"date_updated":"2021-01-12T06:53:47Z","oa_version":"None","publisher":"Springer Nature","title":"Physiology: Relax and come in","day":"23","scopus_import":1,"author":[{"last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","first_name":"Michael K"},{"full_name":"Vaahtomeri, Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","last_name":"Vaahtomeri","first_name":"Kari","orcid":"0000-0001-7829-3518"}],"doi":"10.1038/514441a","publication_status":"published","quality_controlled":"1","intvolume":"       514","abstract":[{"text":"During inflammation, lymph nodes swell with an influx of immune cells. New findings identify a signalling pathway that induces relaxation in the contractile cells that give structure to these organs.","lang":"eng"}],"page":"441 - 442","publist_id":"5219","department":[{"_id":"MiSi"}],"month":"10","year":"2014","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2014-10-23T00:00:00Z","citation":{"short":"M.K. Sixt, K. Vaahtomeri, Nature 514 (2014) 441–442.","ieee":"M. K. Sixt and K. Vaahtomeri, “Physiology: Relax and come in,” <i>Nature</i>, vol. 514, no. 7523. Springer Nature, pp. 441–442, 2014.","ama":"Sixt MK, Vaahtomeri K. Physiology: Relax and come in. <i>Nature</i>. 2014;514(7523):441-442. doi:<a href=\"https://doi.org/10.1038/514441a\">10.1038/514441a</a>","mla":"Sixt, Michael K., and Kari Vaahtomeri. “Physiology: Relax and Come In.” <i>Nature</i>, vol. 514, no. 7523, Springer Nature, 2014, pp. 441–42, doi:<a href=\"https://doi.org/10.1038/514441a\">10.1038/514441a</a>.","apa":"Sixt, M. K., &#38; Vaahtomeri, K. (2014). Physiology: Relax and come in. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/514441a\">https://doi.org/10.1038/514441a</a>","ista":"Sixt MK, Vaahtomeri K. 2014. Physiology: Relax and come in. Nature. 514(7523), 441–442.","chicago":"Sixt, Michael K, and Kari Vaahtomeri. “Physiology: Relax and Come In.” <i>Nature</i>. Springer Nature, 2014. <a href=\"https://doi.org/10.1038/514441a\">https://doi.org/10.1038/514441a</a>."},"issue":"7523","status":"public","publication":"Nature","language":[{"iso":"eng"}]}]