[{"file_date_updated":"2022-07-25T07:11:32Z","ec_funded":1,"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"year":"2022","acknowledgement":"This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.","date_created":"2021-08-06T09:09:11Z","date_updated":"2023-08-02T06:53:07Z","volume":23,"author":[{"full_name":"Assen, Frank P","first_name":"Frank P","last_name":"Assen","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119"},{"full_name":"Abe, Jun","last_name":"Abe","first_name":"Jun"},{"full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","last_name":"Hons","first_name":"Miroslav"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert"},{"full_name":"Shamipour, Shayan","first_name":"Shayan","last_name":"Shamipour","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kaufmann","first_name":"Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","full_name":"Kaufmann, Walter"},{"full_name":"Costanzo, Tommaso","orcid":"0000-0001-9732-3815","id":"D93824F4-D9BA-11E9-BB12-F207E6697425","last_name":"Costanzo","first_name":"Tommaso"},{"first_name":"Gabriel","last_name":"Krens","id":"2B819732-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4761-5996","full_name":"Krens, Gabriel"},{"full_name":"Brown, Markus","first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Ludewig","first_name":"Burkhard","full_name":"Ludewig, Burkhard"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"},{"first_name":"Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J"},{"first_name":"Wolfgang","last_name":"Weninger","full_name":"Weninger, Wolfgang"},{"full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","first_name":"Edouard B","last_name":"Hannezo"},{"last_name":"Luther","first_name":"Sanjiv A.","full_name":"Luther, Sanjiv A."},{"last_name":"Stein","first_name":"Jens V.","full_name":"Stein, Jens V."},{"full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-4561-241X","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"month":"07","publication_identifier":{"eissn":["1529-2916"],"issn":["1529-2908"]},"quality_controlled":"1","isi":1,"project":[{"call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"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","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000822975900002"]},"oa":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41590-022-01257-4","type":"journal_article","abstract":[{"text":"Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.","lang":"eng"}],"ddc":["570"],"status":"public","title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","intvolume":" 23","_id":"9794","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","file":[{"file_id":"11642","relation":"main_file","success":1,"checksum":"628e7b49809f22c75b428842efe70c68","date_created":"2022-07-25T07:11:32Z","date_updated":"2022-07-25T07:11:32Z","access_level":"open_access","file_name":"2022_NatureImmunology_Assen.pdf","creator":"dernst","file_size":11475325,"content_type":"application/pdf"}],"scopus_import":"1","day":"11","has_accepted_license":"1","article_processing_charge":"No","article_type":"original","page":"1246-1255","publication":"Nature Immunology","citation":{"ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4","ieee":"F. P. Assen et al., “Multitier mechanics control stromal adaptations in swelling lymph nodes,” Nature Immunology, vol. 23. Springer Nature, pp. 1246–1255, 2022.","apa":"Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4","ista":"Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255.","short":"F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255.","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:10.1038/s41590-022-01257-4.","chicago":"Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology. Springer Nature, 2022. https://doi.org/10.1038/s41590-022-01257-4."},"date_published":"2022-07-11T00:00:00Z"},{"date_published":"2018-04-12T00:00:00Z","page":"2205 - 2221","citation":{"ieee":"M. Brown et al., “Lymphatic exosomes promote dendritic cell migration along guidance cues,” Journal of Cell Biology, vol. 217, no. 6. Rockefeller University Press, pp. 2205–2221, 2018.","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. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.201612051","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.","ama":"Brown M, Johnson L, Leone D, et al. Lymphatic exosomes promote dendritic cell migration along guidance cues. Journal of Cell Biology. 2018;217(6):2205-2221. doi:10.1083/jcb.201612051","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.” Journal of Cell Biology. Rockefeller University Press, 2018. https://doi.org/10.1083/jcb.201612051.","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.","mla":"Brown, Markus, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration along Guidance Cues.” Journal of Cell Biology, vol. 217, no. 6, Rockefeller University Press, 2018, pp. 2205–21, doi:10.1083/jcb.201612051."},"publication":"Journal of Cell Biology","has_accepted_license":"1","article_processing_charge":"No","day":"12","scopus_import":"1","file":[{"creator":"dernst","content_type":"application/pdf","file_size":2252043,"access_level":"open_access","file_name":"2018_JournalCellBiology_Brown.pdf","checksum":"9c7eba51a35c62da8c13f98120b64df4","date_updated":"2020-07-14T12:45:45Z","date_created":"2018-12-17T12:50:07Z","file_id":"5704","relation":"main_file"}],"oa_version":"Published Version","intvolume":" 217","ddc":["570"],"status":"public","title":"Lymphatic exosomes promote dendritic cell migration along guidance cues","_id":"275","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","issue":"6","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 > 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."}],"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1083/jcb.201612051","project":[{"name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12"},{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"}],"isi":1,"quality_controlled":"1","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","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"pmid":["29650776"],"isi":["000438077800026"]},"month":"04","volume":217,"date_updated":"2023-09-13T08:51:29Z","date_created":"2018-12-11T11:45:33Z","author":[{"first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus"},{"full_name":"Johnson, Louise","last_name":"Johnson","first_name":"Louise"},{"full_name":"Leone, Dario","last_name":"Leone","first_name":"Dario"},{"full_name":"Májek, Peter","last_name":"Májek","first_name":"Peter"},{"full_name":"Vaahtomeri, Kari","last_name":"Vaahtomeri","first_name":"Kari","orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Daniel","last_name":"Senfter","full_name":"Senfter, Daniel"},{"last_name":"Bukosza","first_name":"Nora","full_name":"Bukosza, Nora"},{"full_name":"Schachner, Helga","last_name":"Schachner","first_name":"Helga"},{"full_name":"Asfour, Gabriele","last_name":"Asfour","first_name":"Gabriele"},{"full_name":"Langer, Brigitte","last_name":"Langer","first_name":"Brigitte"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","first_name":"Robert","last_name":"Hauschild","full_name":"Hauschild, Robert"},{"last_name":"Parapatics","first_name":"Katja","full_name":"Parapatics, Katja"},{"first_name":"Young","last_name":"Hong","full_name":"Hong, Young"},{"full_name":"Bennett, Keiryn","last_name":"Bennett","first_name":"Keiryn"},{"full_name":"Kain, Renate","first_name":"Renate","last_name":"Kain"},{"full_name":"Detmar, Michael","first_name":"Michael","last_name":"Detmar"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"},{"full_name":"Jackson, David","last_name":"Jackson","first_name":"David"},{"full_name":"Kerjaschki, Dontscho","last_name":"Kerjaschki","first_name":"Dontscho"}],"department":[{"_id":"MiSi"},{"_id":"Bio"}],"publisher":"Rockefeller University Press","publication_status":"published","pmid":1,"year":"2018","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).","publist_id":"7627","ec_funded":1,"file_date_updated":"2020-07-14T12:45:45Z"},{"article_processing_charge":"No","day":"23","scopus_import":"1","date_published":"2018-03-23T00:00:00Z","citation":{"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.","mla":"Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” Science, vol. 359, no. 6382, American Association for the Advancement of Science, 2018, pp. 1408–11, doi:10.1126/science.aal3662.","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.” Science. American Association for the Advancement of Science, 2018. https://doi.org/10.1126/science.aal3662.","ama":"Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 2018;359(6382):1408-1411. doi:10.1126/science.aal3662","ieee":"M. Brown et al., “Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice,” Science, vol. 359, no. 6382. American Association for the Advancement of Science, pp. 1408–1411, 2018.","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. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aal3662","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."},"publication":"Science","page":"1408 - 1411","article_type":"original","issue":"6382","abstract":[{"text":"During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","_id":"402","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 359","title":"Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice","status":"public","month":"03","doi":"10.1126/science.aal3662","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"}],"oa":1,"external_id":{"isi":["000428043600047"],"pmid":["29567714"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1126/science.aal3662"}],"project":[{"grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)"},{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556"}],"isi":1,"quality_controlled":"1","publist_id":"7428","ec_funded":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"6947"}]},"author":[{"full_name":"Brown, Markus","first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Assen, Frank P","first_name":"Frank P","last_name":"Assen","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119"},{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","first_name":"Alexander F","last_name":"Leithner"},{"first_name":"Jun","last_name":"Abe","full_name":"Abe, Jun"},{"full_name":"Schachner, Helga","last_name":"Schachner","first_name":"Helga"},{"last_name":"Asfour","first_name":"Gabriele","full_name":"Asfour, Gabriele"},{"first_name":"Zsuzsanna","last_name":"Bagó Horváth","full_name":"Bagó Horváth, Zsuzsanna"},{"first_name":"Jens","last_name":"Stein","full_name":"Stein, Jens"},{"last_name":"Uhrin","first_name":"Pavel","full_name":"Uhrin, Pavel"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K"},{"full_name":"Kerjaschki, Dontscho","first_name":"Dontscho","last_name":"Kerjaschki"}],"volume":359,"date_created":"2018-12-11T11:46:16Z","date_updated":"2024-03-28T23:30:09Z","pmid":1,"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.","year":"2018","department":[{"_id":"MiSi"}],"publisher":"American Association for the Advancement of Science","publication_status":"published"},{"date_published":"2017-05-02T00:00:00Z","page":"902 - 909","publication":"Cell Reports","citation":{"chicago":"Vaahtomeri, Kari, Markus Brown, Robert Hauschild, Ingrid de Vries, Alexander F Leithner, Matthias Mehling, Walter Kaufmann, and Michael K Sixt. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2017.04.027.","mla":"Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” Cell Reports, vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:10.1016/j.celrep.2017.04.027.","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.","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.","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. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2017.04.027","ieee":"K. Vaahtomeri et al., “Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia,” Cell Reports, 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. Cell Reports. 2017;19(5):902-909. doi:10.1016/j.celrep.2017.04.027"},"day":"02","article_processing_charge":"Yes","has_accepted_license":"1","scopus_import":1,"oa_version":"Published Version","file":[{"checksum":"8fdddaab1f1d76a6ec9ca94dcb6b07a2","date_updated":"2020-07-14T12:47:38Z","date_created":"2018-12-12T10:14:54Z","relation":"main_file","file_id":"5109","content_type":"application/pdf","file_size":2248814,"creator":"system","access_level":"open_access","file_name":"IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf"}],"pubrep_id":"900","status":"public","ddc":["570"],"title":"Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia","intvolume":" 19","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"672","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"}],"issue":"5","type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1016/j.celrep.2017.04.027","quality_controlled":"1","project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"},{"_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","call_identifier":"FWF"}],"tmp":{"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)","image":"/images/cc_by_nc_nd.png"},"oa":1,"month":"05","publication_identifier":{"issn":["22111247"]},"date_created":"2018-12-11T11:47:50Z","date_updated":"2023-02-23T12:50:09Z","volume":19,"author":[{"full_name":"Vaahtomeri, Kari","last_name":"Vaahtomeri","first_name":"Kari","orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert"},{"full_name":"De Vries, Ingrid","first_name":"Ingrid","last_name":"De Vries","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","first_name":"Alexander F"},{"full_name":"Mehling, Matthias","last_name":"Mehling","first_name":"Matthias","orcid":"0000-0001-8599-1226","id":"3C23B994-F248-11E8-B48F-1D18A9856A87"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","first_name":"Walter","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"publication_status":"published","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}],"publisher":"Cell Press","year":"2017","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","file_date_updated":"2020-07-14T12:47:38Z","publist_id":"7052","ec_funded":1},{"day":"09","scopus_import":1,"date_published":"2017-05-09T00:00:00Z","publication":"Current Biology","citation":{"chicago":"Schwarz, Jan, Veronika Bierbaum, Kari Vaahtomeri, Robert Hauschild, Markus Brown, Ingrid de Vries, Alexander F Leithner, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current Biology. Cell Press, 2017. https://doi.org/10.1016/j.cub.2017.04.004.","mla":"Schwarz, Jan, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current Biology, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:10.1016/j.cub.2017.04.004.","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.","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.","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. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2017.04.004","ieee":"J. Schwarz et al., “Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6,” Current Biology, 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. Current Biology. 2017;27(9):1314-1325. doi:10.1016/j.cub.2017.04.004"},"page":"1314 - 1325","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"}],"issue":"9","type":"journal_article","oa_version":"None","_id":"674","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","title":"Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6","status":"public","intvolume":" 27","month":"05","publication_identifier":{"issn":["09609822"]},"doi":"10.1016/j.cub.2017.04.004","language":[{"iso":"eng"}],"quality_controlled":"1","project":[{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"call_identifier":"FWF","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"publist_id":"7050","ec_funded":1,"author":[{"full_name":"Schwarz, Jan","last_name":"Schwarz","first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bierbaum","first_name":"Veronika","id":"3FD04378-F248-11E8-B48F-1D18A9856A87","full_name":"Bierbaum, Veronika"},{"id":"368EE576-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7829-3518","first_name":"Kari","last_name":"Vaahtomeri","full_name":"Vaahtomeri, Kari"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Brown, Markus","first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"De Vries"},{"full_name":"Leithner, Alexander F","first_name":"Alexander F","last_name":"Leithner","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"id":"35B76592-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0666-8928","first_name":"Anne","last_name":"Reversat","full_name":"Reversat, Anne"},{"id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609","first_name":"Jack","last_name":"Merrin","full_name":"Merrin, Jack"},{"full_name":"Tarrant, Teresa","last_name":"Tarrant","first_name":"Teresa"},{"full_name":"Bollenbach, Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","first_name":"Tobias","last_name":"Bollenbach"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"}],"date_created":"2018-12-11T11:47:51Z","date_updated":"2023-02-23T12:50:44Z","volume":27,"year":"2017","publication_status":"published","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"NanoFab"}],"publisher":"Cell Press"},{"month":"12","doi":"10.1038/ni.3590","language":[{"iso":"eng"}],"main_file_link":[{"url":"https://ora.ox.ac.uk/objects/uuid:f53a464e-1e5b-4f08-a7d8-b6749b852b9d","open_access":"1"}],"oa":1,"quality_controlled":"1","publist_id":"6216","author":[{"last_name":"Martins","first_name":"Rui","full_name":"Martins, Rui"},{"full_name":"Maier, Julia","first_name":"Julia","last_name":"Maier"},{"last_name":"Gorki","first_name":"Anna","full_name":"Gorki, Anna"},{"last_name":"Huber","first_name":"Kilian","full_name":"Huber, Kilian"},{"full_name":"Sharif, Omar","last_name":"Sharif","first_name":"Omar"},{"first_name":"Philipp","last_name":"Starkl","full_name":"Starkl, Philipp"},{"last_name":"Saluzzo","first_name":"Simona","full_name":"Saluzzo, Simona"},{"last_name":"Quattrone","first_name":"Federica","full_name":"Quattrone, Federica"},{"last_name":"Gawish","first_name":"Riem","full_name":"Gawish, Riem"},{"full_name":"Lakovits, Karin","first_name":"Karin","last_name":"Lakovits"},{"full_name":"Aichinger, Michael","last_name":"Aichinger","first_name":"Michael"},{"last_name":"Radic Sarikas","first_name":"Branka","full_name":"Radic Sarikas, Branka"},{"full_name":"Lardeau, Charles","first_name":"Charles","last_name":"Lardeau"},{"first_name":"Anastasiya","last_name":"Hladik","full_name":"Hladik, Anastasiya"},{"first_name":"Ana","last_name":"Korosec","full_name":"Korosec, Ana"},{"full_name":"Brown, Markus","first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Vaahtomeri, Kari","orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87","last_name":"Vaahtomeri","first_name":"Kari"},{"id":"2EDEA62C-F248-11E8-B48F-1D18A9856A87","first_name":"Michelle","last_name":"Duggan","full_name":"Duggan, Michelle"},{"full_name":"Kerjaschki, Dontscho","last_name":"Kerjaschki","first_name":"Dontscho"},{"full_name":"Esterbauer, Harald","first_name":"Harald","last_name":"Esterbauer"},{"last_name":"Colinge","first_name":"Jacques","full_name":"Colinge, Jacques"},{"full_name":"Eisenbarth, Stephanie","first_name":"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","first_name":"Stefan","last_name":"Kubicek"},{"full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"},{"full_name":"Superti Furga, Giulio","last_name":"Superti Furga","first_name":"Giulio"},{"first_name":"Sylvia","last_name":"Knapp","full_name":"Knapp, Sylvia"}],"date_created":"2018-12-11T11:50:22Z","date_updated":"2021-01-12T06:48:36Z","volume":17,"year":"2016","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).","publication_status":"published","publisher":"Nature Publishing Group","department":[{"_id":"MiSi"},{"_id":"PeJo"}],"day":"01","scopus_import":1,"date_published":"2016-12-01T00:00:00Z","publication":"Nature Immunology","citation":{"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.","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. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3590","ieee":"R. Martins et al., “Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions,” Nature Immunology, vol. 17, no. 12. Nature Publishing Group, pp. 1361–1372, 2016.","ama":"Martins R, Maier J, Gorki A, et al. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nature Immunology. 2016;17(12):1361-1372. doi:10.1038/ni.3590","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.” Nature Immunology. Nature Publishing Group, 2016. https://doi.org/10.1038/ni.3590.","mla":"Martins, Rui, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions.” Nature Immunology, vol. 17, no. 12, Nature Publishing Group, 2016, pp. 1361–72, doi:10.1038/ni.3590.","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."},"page":"1361 - 1372","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"}],"issue":"12","type":"journal_article","oa_version":"Submitted Version","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1142","status":"public","title":"Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions","intvolume":" 17"},{"date_published":"2016-10-24T00:00:00Z","page":"1253 - 1259","article_type":"original","citation":{"ama":"Leithner AF, Eichner A, Müller J, et al. Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. 2016;18:1253-1259. doi:10.1038/ncb3426","ista":"Leithner AF, Eichner A, Müller J, Reversat A, Brown M, Schwarz J, Merrin J, De Gorter D, Schur FK, Bayerl J, de Vries I, Wieser S, Hauschild R, Lai F, Moser M, Kerjaschki D, Rottner K, Small V, Stradal T, Sixt MK. 2016. Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. 18, 1253–1259.","ieee":"A. F. Leithner et al., “Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes,” Nature Cell Biology, vol. 18. Nature Publishing Group, pp. 1253–1259, 2016.","apa":"Leithner, A. F., Eichner, A., Müller, J., Reversat, A., Brown, M., Schwarz, J., … Sixt, M. K. (2016). Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. Nature Publishing Group. https://doi.org/10.1038/ncb3426","mla":"Leithner, Alexander F., et al. “Diversified Actin Protrusions Promote Environmental Exploration but Are Dispensable for Locomotion of Leukocytes.” Nature Cell Biology, vol. 18, Nature Publishing Group, 2016, pp. 1253–59, doi:10.1038/ncb3426.","short":"A.F. Leithner, A. Eichner, J. Müller, A. Reversat, M. Brown, J. Schwarz, J. Merrin, D. De Gorter, F.K. Schur, J. Bayerl, I. de Vries, S. Wieser, R. Hauschild, F. Lai, M. Moser, D. Kerjaschki, K. Rottner, V. Small, T. Stradal, M.K. Sixt, Nature Cell Biology 18 (2016) 1253–1259.","chicago":"Leithner, Alexander F, Alexander Eichner, Jan Müller, Anne Reversat, Markus Brown, Jan Schwarz, Jack Merrin, et al. “Diversified Actin Protrusions Promote Environmental Exploration but Are Dispensable for Locomotion of Leukocytes.” Nature Cell Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/ncb3426."},"publication":"Nature Cell Biology","article_processing_charge":"No","has_accepted_license":"1","day":"24","scopus_import":1,"oa_version":"Submitted Version","file":[{"relation":"main_file","file_id":"7844","checksum":"e1411cb7c99a2d9089c178a6abef25e7","date_created":"2020-05-14T16:33:46Z","date_updated":"2020-07-14T12:44:43Z","access_level":"open_access","file_name":"2018_NatureCell_Leithner.pdf","file_size":4433280,"content_type":"application/pdf","creator":"dernst"}],"intvolume":" 18","title":"Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes","status":"public","ddc":["570"],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1321","abstract":[{"lang":"eng","text":"Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion."}],"type":"journal_article","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"SSU"}],"doi":"10.1038/ncb3426","project":[{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556"}],"quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"month":"10","volume":18,"date_updated":"2024-03-28T23:30:16Z","date_created":"2018-12-11T11:51:21Z","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"323"}]},"author":[{"full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","first_name":"Alexander F"},{"last_name":"Eichner","first_name":"Alexander","id":"4DFA52AE-F248-11E8-B48F-1D18A9856A87","full_name":"Eichner, Alexander"},{"full_name":"Müller, Jan","first_name":"Jan","last_name":"Müller","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D"},{"last_name":"Reversat","first_name":"Anne","orcid":"0000-0003-0666-8928","id":"35B76592-F248-11E8-B48F-1D18A9856A87","full_name":"Reversat, Anne"},{"id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","last_name":"Brown","first_name":"Markus","full_name":"Brown, Markus"},{"full_name":"Schwarz, Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Jan"},{"last_name":"Merrin","first_name":"Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","full_name":"Merrin, Jack"},{"first_name":"David","last_name":"De Gorter","full_name":"De Gorter, David"},{"full_name":"Schur, Florian","last_name":"Schur","first_name":"Florian","orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bayerl","first_name":"Jonathan","full_name":"Bayerl, Jonathan"},{"full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid"},{"id":"355AA5A0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2670-2217","first_name":"Stefan","last_name":"Wieser","full_name":"Wieser, Stefan"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert"},{"first_name":"Frank","last_name":"Lai","full_name":"Lai, Frank"},{"first_name":"Markus","last_name":"Moser","full_name":"Moser, Markus"},{"full_name":"Kerjaschki, Dontscho","first_name":"Dontscho","last_name":"Kerjaschki"},{"last_name":"Rottner","first_name":"Klemens","full_name":"Rottner, Klemens"},{"full_name":"Small, Victor","first_name":"Victor","last_name":"Small"},{"last_name":"Stradal","first_name":"Theresia","full_name":"Stradal, Theresia"},{"full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"publisher":"Nature Publishing Group","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"publication_status":"published","acknowledgement":"This work was supported by the German Research Foundation (DFG) Priority Program SP 1464 to T.E.B.S. and M.S., and European Research Council (ERC GA 281556) and Human Frontiers Program grants to M.S.\r\nService Units of IST Austria for excellent technical support.","year":"2016","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","ec_funded":1,"publist_id":"5949","file_date_updated":"2020-07-14T12:44:43Z"},{"year":"2013","_id":"2283","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","publication_status":"published","title":"Tolerating an infection: an indirect benefit of co-founding queen associations in the ant Lasius niger ","intvolume":" 100","department":[{"_id":"SyCr"}],"publisher":"Springer","author":[{"id":"3C7F4840-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1122-3982","first_name":"Christopher","last_name":"Pull","full_name":"Pull, Christopher"},{"first_name":"William","last_name":"Hughes","full_name":"Hughes, William"},{"last_name":"Brown","first_name":"Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus"}],"date_updated":"2021-01-12T06:56:31Z","date_created":"2018-12-11T11:56:45Z","volume":100,"oa_version":"None","type":"journal_article","abstract":[{"lang":"eng","text":"Pathogens exert a strong selection pressure on organisms to evolve effective immune defences. In addition to individual immunity, social organisms can act cooperatively to produce collective defences. In many ant species, queens have the option to found a colony alone or in groups with other, often unrelated, conspecifics. These associations are transient, usually lasting only as long as each queen benefits from the presence of others. In fact, once the first workers emerge, queens fight to the death for dominance. One potential advantage of co-founding may be that queens benefit from collective disease defences, such as mutual grooming, that act against common soil pathogens. We test this hypothesis by exposing single and co-founding queens to a fungal parasite, in order to assess whether queens in co-founding associations have improved survival. Surprisingly, co-foundresses exposed to the entomopathogenic fungus Metarhizium did not engage in cooperative disease defences, and consequently, we find no direct benefit of multiple queens on survival. However, an indirect benefit was observed, with parasite-exposed queens producing more brood when they co-founded, than when they were alone. We suggest this is due to a trade-off between reproduction and immunity. Additionally, we report an extraordinary ability of the queens to tolerate an infection for long periods after parasite exposure. Our study suggests that there are no social immunity benefits for co-founding ant queens, but that in parasite-rich environments, the presence of additional queens may nevertheless improve the chances of colony founding success."}],"publist_id":"4649","issue":"12","publication":"Naturwissenschaften","citation":{"ista":"Pull C, Hughes W, Brown M. 2013. Tolerating an infection: an indirect benefit of co-founding queen associations in the ant Lasius niger . Naturwissenschaften. 100(12), 1125–1136.","apa":"Pull, C., Hughes, W., & Brown, M. (2013). Tolerating an infection: an indirect benefit of co-founding queen associations in the ant Lasius niger . Naturwissenschaften. Springer. https://doi.org/10.1007/s00114-013-1115-5","ieee":"C. Pull, W. Hughes, and M. Brown, “Tolerating an infection: an indirect benefit of co-founding queen associations in the ant Lasius niger ,” Naturwissenschaften, vol. 100, no. 12. Springer, pp. 1125–1136, 2013.","ama":"Pull C, Hughes W, Brown M. Tolerating an infection: an indirect benefit of co-founding queen associations in the ant Lasius niger . Naturwissenschaften. 2013;100(12):1125-1136. doi:10.1007/s00114-013-1115-5","chicago":"Pull, Christopher, William Hughes, and Markus Brown. “Tolerating an Infection: An Indirect Benefit of Co-Founding Queen Associations in the Ant Lasius Niger .” Naturwissenschaften. Springer, 2013. https://doi.org/10.1007/s00114-013-1115-5.","mla":"Pull, Christopher, et al. “Tolerating an Infection: An Indirect Benefit of Co-Founding Queen Associations in the Ant Lasius Niger .” Naturwissenschaften, vol. 100, no. 12, Springer, 2013, pp. 1125–36, doi:10.1007/s00114-013-1115-5.","short":"C. Pull, W. Hughes, M. Brown, Naturwissenschaften 100 (2013) 1125–1136."},"quality_controlled":"1","page":"1125 - 1136","doi":"10.1007/s00114-013-1115-5","date_published":"2013-11-14T00:00:00Z","language":[{"iso":"eng"}],"scopus_import":1,"month":"11","day":"14"}]