---
_id: '9259'
abstract:
- lang: eng
  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.
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."
article_number: '630002'
article_processing_charge: No
article_type: original
author:
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
- first_name: Christine
  full_name: Moussion, Christine
  id: 3356F664-F248-11E8-B48F-1D18A9856A87
  last_name: Moussion
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
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>
  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>
  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>.
  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.
  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.
  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>.
  short: K. Vaahtomeri, C. Moussion, R. Hauschild, M.K. Sixt, Frontiers in Immunology
    12 (2021).
date_created: 2021-03-21T23:01:20Z
date_published: 2021-02-25T00:00:00Z
date_updated: 2023-08-07T14:18:26Z
day: '25'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
doi: 10.3389/fimmu.2021.630002
ec_funded: 1
external_id:
  isi:
  - '000627134400001'
  pmid:
  - '33717158'
file:
- access_level: open_access
  checksum: 663f5a48375e42afa4bfef58d42ec186
  content_type: application/pdf
  creator: dernst
  date_created: 2021-03-22T12:08:26Z
  date_updated: 2021-03-22T12:08:26Z
  file_id: '9277'
  file_name: 2021_FrontiersImmumo_Vaahtomeri.pdf
  file_size: 3740146
  relation: main_file
  success: 1
file_date_updated: 2021-03-22T12:08:26Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular navigation along spatial gradients
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
publication: Frontiers in Immunology
publication_identifier:
  eissn:
  - 1664-3224
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Shape and function of interstitial chemokine CCL21 gradients are independent
  of heparan sulfates produced by lymphatic endothelium
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '275'
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.
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).
article_processing_charge: No
author:
- first_name: Markus
  full_name: Brown, Markus
  id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
  last_name: Brown
- first_name: Louise
  full_name: Johnson, Louise
  last_name: Johnson
- first_name: Dario
  full_name: Leone, Dario
  last_name: Leone
- first_name: Peter
  full_name: Májek, Peter
  last_name: Májek
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
- first_name: Daniel
  full_name: Senfter, Daniel
  last_name: Senfter
- first_name: Nora
  full_name: Bukosza, Nora
  last_name: Bukosza
- first_name: Helga
  full_name: Schachner, Helga
  last_name: Schachner
- first_name: Gabriele
  full_name: Asfour, Gabriele
  last_name: Asfour
- first_name: Brigitte
  full_name: Langer, Brigitte
  last_name: Langer
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Katja
  full_name: Parapatics, Katja
  last_name: Parapatics
- first_name: Young
  full_name: Hong, Young
  last_name: Hong
- first_name: Keiryn
  full_name: Bennett, Keiryn
  last_name: Bennett
- first_name: Renate
  full_name: Kain, Renate
  last_name: Kain
- first_name: Michael
  full_name: Detmar, Michael
  last_name: Detmar
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: David
  full_name: Jackson, David
  last_name: Jackson
- first_name: Dontscho
  full_name: Kerjaschki, Dontscho
  last_name: Kerjaschki
citation:
  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>
  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>.
  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.
  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.
  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>.
  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.
date_created: 2018-12-11T11:45:33Z
date_published: 2018-04-12T00:00:00Z
date_updated: 2023-09-13T08:51:29Z
day: '12'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
doi: 10.1083/jcb.201612051
ec_funded: 1
external_id:
  isi:
  - '000438077800026'
  pmid:
  - '29650776'
file:
- access_level: open_access
  checksum: 9c7eba51a35c62da8c13f98120b64df4
  content_type: application/pdf
  creator: dernst
  date_created: 2018-12-17T12:50:07Z
  date_updated: 2020-07-14T12:45:45Z
  file_id: '5704'
  file_name: 2018_JournalCellBiology_Brown.pdf
  file_size: 2252043
  relation: main_file
file_date_updated: 2020-07-14T12:45:45Z
has_accepted_license: '1'
intvolume: '       217'
isi: 1
issue: '6'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 2205 - 2221
pmid: 1
project:
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and transduction of leukocytes (FWF)
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '281556'
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
    (EU)
publication: Journal of Cell Biology
publication_status: published
publisher: Rockefeller University Press
publist_id: '7627'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Lymphatic exosomes promote dendritic cell migration along guidance cues
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 217
year: '2018'
...
---
_id: '402'
abstract:
- lang: eng
  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.
acknowledged_ssus:
- _id: Bio
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."
article_processing_charge: No
article_type: original
author:
- first_name: Markus
  full_name: Brown, Markus
  id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
  last_name: Brown
- first_name: Frank P
  full_name: Assen, Frank P
  id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
  last_name: Assen
  orcid: 0000-0003-3470-6119
- first_name: Alexander F
  full_name: Leithner, Alexander F
  id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
  last_name: Leithner
  orcid: 0000-0002-1073-744X
- first_name: Jun
  full_name: Abe, Jun
  last_name: Abe
- first_name: Helga
  full_name: Schachner, Helga
  last_name: Schachner
- first_name: Gabriele
  full_name: Asfour, Gabriele
  last_name: Asfour
- first_name: Zsuzsanna
  full_name: Bagó Horváth, Zsuzsanna
  last_name: Bagó Horváth
- first_name: Jens
  full_name: Stein, Jens
  last_name: Stein
- first_name: Pavel
  full_name: Uhrin, Pavel
  last_name: Uhrin
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Dontscho
  full_name: Kerjaschki, Dontscho
  last_name: Kerjaschki
citation:
  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>
  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>
  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>.
  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.
  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>.
  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.
date_created: 2018-12-11T11:46:16Z
date_published: 2018-03-23T00:00:00Z
date_updated: 2024-03-25T23:30:05Z
day: '23'
department:
- _id: MiSi
doi: 10.1126/science.aal3662
ec_funded: 1
external_id:
  isi:
  - '000428043600047'
  pmid:
  - '29567714'
intvolume: '       359'
isi: 1
issue: '6382'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1126/science.aal3662
month: '03'
oa: 1
oa_version: Published Version
page: 1408 - 1411
pmid: 1
project:
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and transduction of leukocytes (FWF)
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '281556'
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
    (EU)
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '7428'
quality_controlled: '1'
related_material:
  record:
  - id: '6947'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination
  in mice
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 359
year: '2018'
...
---
_id: '672'
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
author:
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
- first_name: Markus
  full_name: Brown, Markus
  id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
  last_name: Brown
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Ingrid
  full_name: De Vries, Ingrid
  id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
  last_name: De Vries
- first_name: Alexander F
  full_name: Leithner, Alexander F
  id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
  last_name: Leithner
- first_name: Matthias
  full_name: Mehling, Matthias
  id: 3C23B994-F248-11E8-B48F-1D18A9856A87
  last_name: Mehling
  orcid: 0000-0001-8599-1226
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  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>
  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>
  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>.
  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.
  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.
  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>.
  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.
date_created: 2018-12-11T11:47:50Z
date_published: 2017-05-02T00:00:00Z
date_updated: 2023-02-23T12:50:09Z
day: '02'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
- _id: EM-Fac
doi: 10.1016/j.celrep.2017.04.027
ec_funded: 1
file:
- access_level: open_access
  checksum: 8fdddaab1f1d76a6ec9ca94dcb6b07a2
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:14:54Z
  date_updated: 2020-07-14T12:47:38Z
  file_id: '5109'
  file_name: IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf
  file_size: 2248814
  relation: main_file
file_date_updated: 2020-07-14T12:47:38Z
has_accepted_license: '1'
intvolume: '        19'
issue: '5'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '05'
oa: 1
oa_version: Published Version
page: 902 - 909
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
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Cell Reports
publication_identifier:
  issn:
  - '22111247'
publication_status: published
publisher: Cell Press
publist_id: '7052'
pubrep_id: '900'
quality_controlled: '1'
scopus_import: 1
status: public
title: Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration
  across lymphatic endothelia
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 19
year: '2017'
...
---
_id: '674'
abstract:
- lang: eng
  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.
author:
- first_name: Jan
  full_name: Schwarz, Jan
  id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Veronika
  full_name: Bierbaum, Veronika
  id: 3FD04378-F248-11E8-B48F-1D18A9856A87
  last_name: Bierbaum
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Markus
  full_name: Brown, Markus
  id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
  last_name: Brown
- first_name: Ingrid
  full_name: De Vries, Ingrid
  id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
  last_name: De Vries
- first_name: Alexander F
  full_name: Leithner, Alexander F
  id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
  last_name: Leithner
- first_name: Anne
  full_name: Reversat, Anne
  id: 35B76592-F248-11E8-B48F-1D18A9856A87
  last_name: Reversat
  orcid: 0000-0003-0666-8928
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Teresa
  full_name: Tarrant, Teresa
  last_name: Tarrant
- first_name: Tobias
  full_name: Bollenbach, Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  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>
  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>
  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>.
  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.
  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.
  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>.
  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.
date_created: 2018-12-11T11:47:51Z
date_published: 2017-05-09T00:00:00Z
date_updated: 2023-02-23T12:50:44Z
day: '09'
department:
- _id: MiSi
- _id: Bio
- _id: NanoFab
doi: 10.1016/j.cub.2017.04.004
ec_funded: 1
intvolume: '        27'
issue: '9'
language:
- iso: eng
month: '05'
oa_version: None
page: 1314 - 1325
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Current Biology
publication_identifier:
  issn:
  - '09609822'
publication_status: published
publisher: Cell Press
publist_id: '7050'
quality_controlled: '1'
scopus_import: 1
status: public
title: Dendritic cells interpret haptotactic chemokine gradients in a manner governed
  by signal to noise ratio and dependent on GRK6
type: journal_article
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 27
year: '2017'
...
---
_id: '1154'
abstract:
- lang: eng
  text: "Cellular locomotion is a central hallmark of eukaryotic life. It is governed
    by cell-extrinsic molecular factors, which can either emerge in the soluble phase
    or as immobilized, often adhesive ligands. To encode for direction, every cue
    must be present as a spatial or temporal gradient. Here, we developed a microfluidic
    chamber that allows measurement of cell migration in combined response to surface
    immobilized and soluble molecular gradients. As a proof of principle we study
    the response of dendritic cells to their major guidance cues, chemokines. The
    majority of data on chemokine gradient sensing is based on in vitro studies employing
    soluble gradients. Despite evidence suggesting that in vivo chemokines are often
    immobilized to sugar residues, limited information is available how cells respond
    to immobilized chemokines. We tracked migration of dendritic cells towards immobilized
    gradients of the chemokine CCL21 and varying superimposed soluble gradients of
    CCL19. Differential migratory patterns illustrate the potential of our setup to
    quantitatively study the competitive response to both types of gradients. Beyond
    chemokines our approach is broadly applicable to alternative systems of chemo-
    and haptotaxis such as cells migrating along gradients of adhesion receptor ligands
    vs. any soluble cue. \r\n"
acknowledgement: 'This work was supported by the Swiss National Science Foundation
  (Ambizione fellowship; PZ00P3-154733 to M.M.), the Swiss Multiple Sclerosis Society
  (research support to M.M.), a fellowship from the Boehringer Ingelheim Fonds (BIF)
  to J.S., the European Research Council (grant ERC GA 281556) and a START award from
  the Austrian Science Foundation (FWF) to M.S. #BioimagingFacility'
article_number: '36440'
author:
- first_name: Jan
  full_name: Schwarz, Jan
  id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Veronika
  full_name: Bierbaum, Veronika
  id: 3FD04378-F248-11E8-B48F-1D18A9856A87
  last_name: Bierbaum
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Tino
  full_name: Frank, Tino
  last_name: Frank
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
- first_name: Savaş
  full_name: Tay, Savaş
  last_name: Tay
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Matthias
  full_name: Mehling, Matthias
  id: 3C23B994-F248-11E8-B48F-1D18A9856A87
  last_name: Mehling
  orcid: 0000-0001-8599-1226
citation:
  ama: Schwarz J, Bierbaum V, Merrin J, et al. A microfluidic device for measuring
    cell migration towards substrate bound and soluble chemokine gradients. <i>Scientific
    Reports</i>. 2016;6. doi:<a href="https://doi.org/10.1038/srep36440">10.1038/srep36440</a>
  apa: Schwarz, J., Bierbaum, V., Merrin, J., Frank, T., Hauschild, R., Bollenbach,
    M. T., … Mehling, M. (2016). A microfluidic device for measuring cell migration
    towards substrate bound and soluble chemokine gradients. <i>Scientific Reports</i>.
    Nature Publishing Group. <a href="https://doi.org/10.1038/srep36440">https://doi.org/10.1038/srep36440</a>
  chicago: Schwarz, Jan, Veronika Bierbaum, Jack Merrin, Tino Frank, Robert Hauschild,
    Mark Tobias Bollenbach, Savaş Tay, Michael K Sixt, and Matthias Mehling. “A Microfluidic
    Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine
    Gradients.” <i>Scientific Reports</i>. Nature Publishing Group, 2016. <a href="https://doi.org/10.1038/srep36440">https://doi.org/10.1038/srep36440</a>.
  ieee: J. Schwarz <i>et al.</i>, “A microfluidic device for measuring cell migration
    towards substrate bound and soluble chemokine gradients,” <i>Scientific Reports</i>,
    vol. 6. Nature Publishing Group, 2016.
  ista: Schwarz J, Bierbaum V, Merrin J, Frank T, Hauschild R, Bollenbach MT, Tay
    S, Sixt MK, Mehling M. 2016. A microfluidic device for measuring cell migration
    towards substrate bound and soluble chemokine gradients. Scientific Reports. 6,
    36440.
  mla: Schwarz, Jan, et al. “A Microfluidic Device for Measuring Cell Migration towards
    Substrate Bound and Soluble Chemokine Gradients.” <i>Scientific Reports</i>, vol.
    6, 36440, Nature Publishing Group, 2016, doi:<a href="https://doi.org/10.1038/srep36440">10.1038/srep36440</a>.
  short: J. Schwarz, V. Bierbaum, J. Merrin, T. Frank, R. Hauschild, M.T. Bollenbach,
    S. Tay, M.K. Sixt, M. Mehling, Scientific Reports 6 (2016).
date_created: 2018-12-11T11:50:27Z
date_published: 2016-11-07T00:00:00Z
date_updated: 2021-01-12T06:48:41Z
day: '07'
ddc:
- '579'
department:
- _id: MiSi
- _id: NanoFab
- _id: Bio
- _id: ToBo
doi: 10.1038/srep36440
ec_funded: 1
file:
- access_level: open_access
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:09:32Z
  date_updated: 2018-12-12T10:09:32Z
  file_id: '4756'
  file_name: IST-2017-744-v1+1_srep36440.pdf
  file_size: 2353456
  relation: main_file
file_date_updated: 2018-12-12T10:09:32Z
has_accepted_license: '1'
intvolume: '         6'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
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
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Scientific Reports
publication_status: published
publisher: Nature Publishing Group
publist_id: '6204'
pubrep_id: '744'
quality_controlled: '1'
scopus_import: 1
status: public
title: A microfluidic device for measuring cell migration towards substrate bound
  and soluble chemokine gradients
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 6
year: '2016'
...
---
_id: '1597'
abstract:
- lang: eng
  text: Chemokines are the main guidance cues directing leukocyte migration. Opposed
    to early assumptions, chemokines do not necessarily act as soluble cues but are
    often immobilized within tissues, e.g., dendritic cell migration toward lymphatic
    vessels is guided by a haptotactic gradient of the chemokine CCL21. Controlled
    assay systems to quantitatively study haptotaxis in vitro are still missing. In
    this chapter, we describe an in vitro haptotaxis assay optimized for the unique
    properties of dendritic cells. The chemokine CCL21 is immobilized in a bioactive
    state, using laser-assisted protein adsorption by photobleaching. The cells follow
    this immobilized CCL21 gradient in a haptotaxis chamber, which provides three
    dimensionally confined migration conditions.
acknowledged_ssus:
- _id: Bio
acknowledgement: This work was supported by the Boehringer Ingelheim Fonds, the European
  Research Council (ERC StG 281556), and a START Award of the Austrian Science Foundation
  (FWF). We thank Robert Hauschild, Anne Reversat, and Jack Merrin for valuable input
  and the Imaging Facility of IST Austria for excellent support.
article_processing_charge: No
article_type: original
author:
- first_name: Jan
  full_name: Schwarz, Jan
  id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  ama: Schwarz J, Sixt MK. Quantitative analysis of dendritic cell haptotaxis. <i>Methods
    in Enzymology</i>. 2016;570:567-581. doi:<a href="https://doi.org/10.1016/bs.mie.2015.11.004">10.1016/bs.mie.2015.11.004</a>
  apa: Schwarz, J., &#38; Sixt, M. K. (2016). Quantitative analysis of dendritic cell
    haptotaxis. <i>Methods in Enzymology</i>. Elsevier. <a href="https://doi.org/10.1016/bs.mie.2015.11.004">https://doi.org/10.1016/bs.mie.2015.11.004</a>
  chicago: Schwarz, Jan, and Michael K Sixt. “Quantitative Analysis of Dendritic Cell
    Haptotaxis.” <i>Methods in Enzymology</i>. Elsevier, 2016. <a href="https://doi.org/10.1016/bs.mie.2015.11.004">https://doi.org/10.1016/bs.mie.2015.11.004</a>.
  ieee: J. Schwarz and M. K. Sixt, “Quantitative analysis of dendritic cell haptotaxis,”
    <i>Methods in Enzymology</i>, vol. 570. Elsevier, pp. 567–581, 2016.
  ista: Schwarz J, Sixt MK. 2016. Quantitative analysis of dendritic cell haptotaxis.
    Methods in Enzymology. 570, 567–581.
  mla: Schwarz, Jan, and Michael K. Sixt. “Quantitative Analysis of Dendritic Cell
    Haptotaxis.” <i>Methods in Enzymology</i>, vol. 570, Elsevier, 2016, pp. 567–81,
    doi:<a href="https://doi.org/10.1016/bs.mie.2015.11.004">10.1016/bs.mie.2015.11.004</a>.
  short: J. Schwarz, M.K. Sixt, Methods in Enzymology 570 (2016) 567–581.
date_created: 2018-12-11T11:52:56Z
date_published: 2016-01-01T00:00:00Z
date_updated: 2021-01-12T06:51:51Z
day: '01'
department:
- _id: MiSi
doi: 10.1016/bs.mie.2015.11.004
ec_funded: 1
external_id:
  pmid:
  - '26921962'
intvolume: '       570'
language:
- iso: eng
month: '01'
oa_version: None
page: 567 - 581
pmid: 1
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
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Methods in Enzymology
publication_status: published
publisher: Elsevier
publist_id: '5573'
quality_controlled: '1'
scopus_import: 1
status: public
title: Quantitative analysis of dendritic cell haptotaxis
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 570
year: '2016'
...
---
_id: '1599'
abstract:
- lang: eng
  text: "The addition of polysialic acid to N- and/or O-linked glycans, referred to
    as polysialylation, is a rare posttranslational modification that is mainly known
    to control the developmental plasticity of the nervous system. Here we show that
    CCR7, the central chemokine receptor controlling immune cell trafficking to secondary
    lymphatic organs, carries polysialic acid. This modification is essential for
    the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking
    is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed
    lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function
    analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited
    conformation, which is released upon interaction with polysialic acid. Thus, we
    describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic
    basis.\r\n"
acknowledged_ssus:
- _id: SSU
acknowledgement: 'We thank S. Schüchner and E. Ogris for kindly providing the antibody
  to GFP, M. Helmbrecht and A. Huber for providing Nrp2−/− mice, the IST Scientific
  Support Facilities for excellent services, and J. Renkawitz and K. Vaahtomeri for
  critically reading the manuscript. '
article_processing_charge: No
article_type: original
author:
- first_name: Eva
  full_name: Kiermaier, Eva
  id: 3EB04B78-F248-11E8-B48F-1D18A9856A87
  last_name: Kiermaier
  orcid: 0000-0001-6165-5738
- first_name: Christine
  full_name: Moussion, Christine
  id: 3356F664-F248-11E8-B48F-1D18A9856A87
  last_name: Moussion
- first_name: Christopher
  full_name: Veldkamp, Christopher
  last_name: Veldkamp
- first_name: Rita
  full_name: Gerardy  Schahn, Rita
  last_name: Gerardy  Schahn
- first_name: Ingrid
  full_name: De Vries, Ingrid
  id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
  last_name: De Vries
- first_name: Larry
  full_name: Williams, Larry
  last_name: Williams
- first_name: Gary
  full_name: Chaffee, Gary
  last_name: Chaffee
- first_name: Andrew
  full_name: Phillips, Andrew
  last_name: Phillips
- first_name: Friedrich
  full_name: Freiberger, Friedrich
  last_name: Freiberger
- first_name: Richard
  full_name: Imre, Richard
  last_name: Imre
- first_name: Deni
  full_name: Taleski, Deni
  last_name: Taleski
- first_name: Richard
  full_name: Payne, Richard
  last_name: Payne
- first_name: Asolina
  full_name: Braun, Asolina
  last_name: Braun
- first_name: Reinhold
  full_name: Förster, Reinhold
  last_name: Förster
- first_name: Karl
  full_name: Mechtler, Karl
  last_name: Mechtler
- first_name: Martina
  full_name: Mühlenhoff, Martina
  last_name: Mühlenhoff
- first_name: Brian
  full_name: Volkman, Brian
  last_name: Volkman
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  ama: Kiermaier E, Moussion C, Veldkamp C, et al. Polysialylation controls dendritic
    cell trafficking by regulating chemokine recognition. <i>Science</i>. 2016;351(6269):186-190.
    doi:<a href="https://doi.org/10.1126/science.aad0512">10.1126/science.aad0512</a>
  apa: Kiermaier, E., Moussion, C., Veldkamp, C., Gerardy  Schahn, R., de Vries, I.,
    Williams, L., … Sixt, M. K. (2016). Polysialylation controls dendritic cell trafficking
    by regulating chemokine recognition. <i>Science</i>. American Association for
    the Advancement of Science. <a href="https://doi.org/10.1126/science.aad0512">https://doi.org/10.1126/science.aad0512</a>
  chicago: Kiermaier, Eva, Christine Moussion, Christopher Veldkamp, Rita Gerardy 
    Schahn, Ingrid de Vries, Larry Williams, Gary Chaffee, et al. “Polysialylation
    Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” <i>Science</i>.
    American Association for the Advancement of Science, 2016. <a href="https://doi.org/10.1126/science.aad0512">https://doi.org/10.1126/science.aad0512</a>.
  ieee: E. Kiermaier <i>et al.</i>, “Polysialylation controls dendritic cell trafficking
    by regulating chemokine recognition,” <i>Science</i>, vol. 351, no. 6269. American
    Association for the Advancement of Science, pp. 186–190, 2016.
  ista: Kiermaier E, Moussion C, Veldkamp C, Gerardy  Schahn R, de Vries I, Williams
    L, Chaffee G, Phillips A, Freiberger F, Imre R, Taleski D, Payne R, Braun A, Förster
    R, Mechtler K, Mühlenhoff M, Volkman B, Sixt MK. 2016. Polysialylation controls
    dendritic cell trafficking by regulating chemokine recognition. Science. 351(6269),
    186–190.
  mla: Kiermaier, Eva, et al. “Polysialylation Controls Dendritic Cell Trafficking
    by Regulating Chemokine Recognition.” <i>Science</i>, vol. 351, no. 6269, American
    Association for the Advancement of Science, 2016, pp. 186–90, doi:<a href="https://doi.org/10.1126/science.aad0512">10.1126/science.aad0512</a>.
  short: E. Kiermaier, C. Moussion, C. Veldkamp, R. Gerardy  Schahn, I. de Vries,
    L. Williams, G. Chaffee, A. Phillips, F. Freiberger, R. Imre, D. Taleski, R. Payne,
    A. Braun, R. Förster, K. Mechtler, M. Mühlenhoff, B. Volkman, M.K. Sixt, Science
    351 (2016) 186–190.
date_created: 2018-12-11T11:52:57Z
date_published: 2016-01-08T00:00:00Z
date_updated: 2021-01-12T06:51:52Z
day: '08'
department:
- _id: MiSi
doi: 10.1126/science.aad0512
ec_funded: 1
external_id:
  pmid:
  - '26657283'
intvolume: '       351'
issue: '6269'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583642/
month: '01'
oa: 1
oa_version: Submitted Version
page: 186 - 190
pmid: 1
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: 25A76F58-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '289720'
  name: Stromal Cell-immune Cell Interactions in Health and Disease
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '5570'
quality_controlled: '1'
scopus_import: 1
status: public
title: Polysialylation controls dendritic cell trafficking by regulating chemokine
  recognition
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 351
year: '2016'
...
---
_id: '1285'
abstract:
- lang: eng
  text: Cell migration is central to a multitude of physiological processes, including
    embryonic development, immune surveillance, and wound healing, and deregulated
    migration is key to cancer dissemination. Decades of investigations have uncovered
    many of the molecular and physical mechanisms underlying cell migration. Together
    with protrusion extension and cell body retraction, adhesion to the substrate
    via specific focal adhesion points has long been considered an essential step
    in cell migration. Although this is true for cells moving on two-dimensional substrates,
    recent studies have demonstrated that focal adhesions are not required for cells
    moving in three dimensions, in which confinement is sufficient to maintain a cell
    in contact with its substrate. Here, we review the investigations that have led
    to challenging the requirement of specific adhesions for migration, discuss the
    physical mechanisms proposed for cell body translocation during focal adhesion-independent
    migration, and highlight the remaining open questions for the future.
acknowledgement: We would like to thank Dani Bodor for critical comments on the manuscript
  and Guillaume Salbreux for discussions. The authors are supported by the United
  Kingdom's Medical Research Council (MRC) (E.K.P. and I.M.A.; core funding to the
  MRC Laboratory for Molecular Cell Biology), by the European Research Council [ERC
  GA 311637 (E.K.P.) and ERC GA 281556 (M.S.)], and by a START award from the Austrian
  Science Foundation (M.S.).
author:
- first_name: Ewa
  full_name: Paluch, Ewa
  last_name: Paluch
- first_name: Irene
  full_name: Aspalter, Irene
  last_name: Aspalter
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  ama: Paluch E, Aspalter I, Sixt MK. Focal adhesion-independent cell migration. <i>Annual
    Review of Cell and Developmental Biology</i>. 2016;32:469-490. doi:<a href="https://doi.org/10.1146/annurev-cellbio-111315-125341">10.1146/annurev-cellbio-111315-125341</a>
  apa: Paluch, E., Aspalter, I., &#38; Sixt, M. K. (2016). Focal adhesion-independent
    cell migration. <i>Annual Review of Cell and Developmental Biology</i>. Annual
    Reviews. <a href="https://doi.org/10.1146/annurev-cellbio-111315-125341">https://doi.org/10.1146/annurev-cellbio-111315-125341</a>
  chicago: Paluch, Ewa, Irene Aspalter, and Michael K Sixt. “Focal Adhesion-Independent
    Cell Migration.” <i>Annual Review of Cell and Developmental Biology</i>. Annual
    Reviews, 2016. <a href="https://doi.org/10.1146/annurev-cellbio-111315-125341">https://doi.org/10.1146/annurev-cellbio-111315-125341</a>.
  ieee: E. Paluch, I. Aspalter, and M. K. Sixt, “Focal adhesion-independent cell migration,”
    <i>Annual Review of Cell and Developmental Biology</i>, vol. 32. Annual Reviews,
    pp. 469–490, 2016.
  ista: Paluch E, Aspalter I, Sixt MK. 2016. Focal adhesion-independent cell migration.
    Annual Review of Cell and Developmental Biology. 32, 469–490.
  mla: Paluch, Ewa, et al. “Focal Adhesion-Independent Cell Migration.” <i>Annual
    Review of Cell and Developmental Biology</i>, vol. 32, Annual Reviews, 2016, pp.
    469–90, doi:<a href="https://doi.org/10.1146/annurev-cellbio-111315-125341">10.1146/annurev-cellbio-111315-125341</a>.
  short: E. Paluch, I. Aspalter, M.K. Sixt, Annual Review of Cell and Developmental
    Biology 32 (2016) 469–490.
date_created: 2018-12-11T11:51:08Z
date_published: 2016-10-06T00:00:00Z
date_updated: 2021-01-12T06:49:37Z
day: '06'
department:
- _id: MiSi
doi: 10.1146/annurev-cellbio-111315-125341
ec_funded: 1
intvolume: '        32'
language:
- iso: eng
month: '10'
oa_version: None
page: 469 - 490
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
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Annual Review of Cell and Developmental Biology
publication_status: published
publisher: Annual Reviews
publist_id: '6031'
quality_controlled: '1'
scopus_import: 1
status: public
title: Focal adhesion-independent cell migration
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 32
year: '2016'
...
