[{"publication_identifier":{"issn":["1529-2908"],"eissn":["1529-2916"]},"month":"07","doi":"10.1038/s41590-022-01257-4","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"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":{"isi":["000822975900002"]},"project":[{"call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","isi":1,"ec_funded":1,"file_date_updated":"2022-07-25T07:11:32Z","author":[{"full_name":"Assen, Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119","first_name":"Frank P","last_name":"Assen"},{"last_name":"Abe","first_name":"Jun","full_name":"Abe, Jun"},{"id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","first_name":"Miroslav","last_name":"Hons","full_name":"Hons, Miroslav"},{"last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert"},{"full_name":"Shamipour, Shayan","first_name":"Shayan","last_name":"Shamipour","id":"40B34FE2-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"},{"full_name":"Costanzo, Tommaso","id":"D93824F4-D9BA-11E9-BB12-F207E6697425","orcid":"0000-0001-9732-3815","first_name":"Tommaso","last_name":"Costanzo"},{"full_name":"Krens, Gabriel","last_name":"Krens","first_name":"Gabriel","orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Brown, Markus","first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Burkhard","last_name":"Ludewig","full_name":"Ludewig, Burkhard"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon"},{"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","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","first_name":"Edouard B"},{"first_name":"Sanjiv A.","last_name":"Luther","full_name":"Luther, Sanjiv A."},{"first_name":"Jens V.","last_name":"Stein","full_name":"Stein, Jens V."},{"orcid":"0000-0002-4561-241X","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K"}],"volume":23,"date_updated":"2023-08-02T06:53:07Z","date_created":"2021-08-06T09:09:11Z","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.","year":"2022","department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"publisher":"Springer Nature","publication_status":"published","article_processing_charge":"No","has_accepted_license":"1","day":"11","scopus_import":"1","date_published":"2022-07-11T00:00:00Z","citation":{"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.","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.","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.","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","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.","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","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."},"publication":"Nature Immunology","page":"1246-1255","article_type":"original","abstract":[{"lang":"eng","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."}],"type":"journal_article","file":[{"file_id":"11642","relation":"main_file","success":1,"checksum":"628e7b49809f22c75b428842efe70c68","date_updated":"2022-07-25T07:11:32Z","date_created":"2022-07-25T07:11:32Z","access_level":"open_access","file_name":"2022_NatureImmunology_Assen.pdf","creator":"dernst","content_type":"application/pdf","file_size":11475325}],"oa_version":"Published Version","_id":"9794","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 23","status":"public","title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","ddc":["570"]},{"project":[{"grant_number":"747687","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells"},{"grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Cellular navigation along spatial gradients"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000768933800005"],"pmid":["34919802"]},"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"},"main_file_link":[{"open_access":"1","url":"https://www.sciencedirect.com/science/article/pii/S1534580721009497"}],"oa":1,"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"doi":"10.1016/j.devcel.2021.11.024","publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"month":"01","publisher":"Cell Press ; Elsevier","department":[{"_id":"MiSi"},{"_id":"EM-Fac"},{"_id":"NanoFab"},{"_id":"BjHo"}],"publication_status":"published","pmid":1,"acknowledgement":"We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll for advice on fluorescent labeling of collagen gels. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron Microscopy Facility. This work was funded by grants from the European Research Council ( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 747687.","year":"2022","volume":57,"date_updated":"2024-03-28T23:30:23Z","date_created":"2022-01-30T23:01:33Z","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12726"},{"relation":"dissertation_contains","status":"public","id":"14530"},{"status":"public","relation":"dissertation_contains","id":"12401"}]},"author":[{"full_name":"Gaertner, Florian","first_name":"Florian","last_name":"Gaertner"},{"first_name":"Patricia","last_name":"Reis-Rodrigues","full_name":"Reis-Rodrigues, Patricia"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid"},{"first_name":"Miroslav","last_name":"Hons","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav"},{"first_name":"Juan","last_name":"Aguilera","full_name":"Aguilera, Juan"},{"full_name":"Riedl, Michael","first_name":"Michael","last_name":"Riedl","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4844-6311"},{"orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","first_name":"Alexander F","full_name":"Leithner, Alexander F"},{"last_name":"Tasciyan","first_name":"Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren"},{"full_name":"Kopf, Aglaja","first_name":"Aglaja","last_name":"Kopf","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2187-6656"},{"full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","first_name":"Jack"},{"orcid":"0000-0002-9438-4783","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","last_name":"Zheden","first_name":"Vanessa","full_name":"Zheden, Vanessa"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","first_name":"Walter","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"}],"ec_funded":1,"page":"47-62.e9","article_type":"original","citation":{"chicago":"Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons, Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell. Cell Press ; Elsevier, 2022. https://doi.org/10.1016/j.devcel.2021.11.024.","mla":"Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell, vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:10.1016/j.devcel.2021.11.024.","short":"F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl, A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild, M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9.","ista":"Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK. 2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 57(1), 47–62.e9.","ieee":"F. Gaertner et al., “WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues,” Developmental Cell, vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022.","apa":"Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl, M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. Cell Press ; Elsevier. https://doi.org/10.1016/j.devcel.2021.11.024","ama":"Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 2022;57(1):47-62.e9. doi:10.1016/j.devcel.2021.11.024"},"publication":"Developmental Cell","date_published":"2022-01-10T00:00:00Z","scopus_import":"1","article_processing_charge":"No","day":"10","intvolume":" 57","status":"public","title":"WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10703","oa_version":"Published Version","type":"journal_article","issue":"1","abstract":[{"text":"When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.","lang":"eng"}]},{"month":"06","publication_identifier":{"issn":["00280836"],"eissn":["14764687"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41586-020-2283-z","isi":1,"quality_controlled":"1","project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","call_identifier":"FP7"},{"grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular navigation along spatial gradients","call_identifier":"H2020"},{"_id":"26018E70-B435-11E9-9278-68D0E5697425","grant_number":"P29911","name":"Mechanical adaptation of lamellipodial actin","call_identifier":"FWF"},{"_id":"260AA4E2-B435-11E9-9278-68D0E5697425","grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020"}],"external_id":{"isi":["000532688300008"]},"ec_funded":1,"date_created":"2020-05-24T22:01:01Z","date_updated":"2024-03-28T23:30:24Z","volume":582,"author":[{"orcid":"0000-0003-0666-8928","id":"35B76592-F248-11E8-B48F-1D18A9856A87","last_name":"Reversat","first_name":"Anne","full_name":"Reversat, Anne"},{"full_name":"Gärtner, Florian R","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","last_name":"Gärtner","first_name":"Florian R"},{"full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","first_name":"Jack"},{"full_name":"Stopp, Julian A","last_name":"Stopp","first_name":"Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tasciyan","first_name":"Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren"},{"id":"2A67C376-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2862-8372","first_name":"Juan L","last_name":"Aguilera Servin","full_name":"Aguilera Servin, Juan L"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid"},{"full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert"},{"full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","last_name":"Hons","first_name":"Miroslav"},{"last_name":"Piel","first_name":"Matthieu","full_name":"Piel, Matthieu"},{"first_name":"Andrew","last_name":"Callan-Jones","full_name":"Callan-Jones, Andrew"},{"full_name":"Voituriez, Raphael","last_name":"Voituriez","first_name":"Raphael"},{"full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"14697"},{"relation":"dissertation_contains","status":"public","id":"12401"}],"link":[{"url":"https://ist.ac.at/en/news/off-road-mode-enables-mobile-cells-to-move-freely/","relation":"press_release","description":"News on IST Homepage"}]},"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"MiSi"}],"acknowledgement":"We thank A. Leithner and J. Renkawitz for discussion and critical reading of the manuscript; J. Schwarz and M. Mehling for establishing the microfluidic setups; the Bioimaging Facility of IST Austria for excellent support, as well as the Life Science Facility and the Miba Machine Shop of IST Austria; and F. N. Arslan, L. E. Burnett and L. Li for their work during their rotation in the IST PhD programme. This work was supported by the European Research Council (ERC StG 281556 and CoG 724373) to M.S. and grants from the Austrian Science Fund (FWF P29911) and the WWTF to M.S. M.H. was supported by the European Regional Development Fund Project (CZ.02.1.01/0.0/0.0/15_003/0000476). F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687.","year":"2020","day":"25","article_processing_charge":"No","scopus_import":"1","date_published":"2020-06-25T00:00:00Z","article_type":"original","page":"582–585","publication":"Nature","citation":{"short":"A. Reversat, F.R. Gärtner, J. Merrin, J.A. Stopp, S. Tasciyan, J.L. Aguilera Servin, I. de Vries, R. Hauschild, M. Hons, M. Piel, A. Callan-Jones, R. Voituriez, M.K. Sixt, Nature 582 (2020) 582–585.","mla":"Reversat, Anne, et al. “Cellular Locomotion Using Environmental Topography.” Nature, vol. 582, Springer Nature, 2020, pp. 582–585, doi:10.1038/s41586-020-2283-z.","chicago":"Reversat, Anne, Florian R Gärtner, Jack Merrin, Julian A Stopp, Saren Tasciyan, Juan L Aguilera Servin, Ingrid de Vries, et al. “Cellular Locomotion Using Environmental Topography.” Nature. Springer Nature, 2020. https://doi.org/10.1038/s41586-020-2283-z.","ama":"Reversat A, Gärtner FR, Merrin J, et al. Cellular locomotion using environmental topography. Nature. 2020;582:582–585. doi:10.1038/s41586-020-2283-z","apa":"Reversat, A., Gärtner, F. R., Merrin, J., Stopp, J. A., Tasciyan, S., Aguilera Servin, J. L., … Sixt, M. K. (2020). Cellular locomotion using environmental topography. Nature. Springer Nature. https://doi.org/10.1038/s41586-020-2283-z","ieee":"A. Reversat et al., “Cellular locomotion using environmental topography,” Nature, vol. 582. Springer Nature, pp. 582–585, 2020.","ista":"Reversat A, Gärtner FR, Merrin J, Stopp JA, Tasciyan S, Aguilera Servin JL, de Vries I, Hauschild R, Hons M, Piel M, Callan-Jones A, Voituriez R, Sixt MK. 2020. Cellular locomotion using environmental topography. Nature. 582, 582–585."},"abstract":[{"text":"Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces1. Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour.","lang":"eng"}],"type":"journal_article","oa_version":"None","title":"Cellular locomotion using environmental topography","status":"public","intvolume":" 582","_id":"7885","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"article_processing_charge":"No","day":"18","scopus_import":"1","date_published":"2018-05-18T00:00:00Z","citation":{"ista":"Hons M, Kopf A, Hauschild R, Leithner AF, Gärtner FR, Abe J, Renkawitz J, Stein J, Sixt MK. 2018. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 19(6), 606–616.","apa":"Hons, M., Kopf, A., Hauschild, R., Leithner, A. F., Gärtner, F. R., Abe, J., … Sixt, M. K. (2018). Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/s41590-018-0109-z","ieee":"M. Hons et al., “Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells,” Nature Immunology, vol. 19, no. 6. Nature Publishing Group, pp. 606–616, 2018.","ama":"Hons M, Kopf A, Hauschild R, et al. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 2018;19(6):606-616. doi:10.1038/s41590-018-0109-z","chicago":"Hons, Miroslav, Aglaja Kopf, Robert Hauschild, Alexander F Leithner, Florian R Gärtner, Jun Abe, Jörg Renkawitz, Jens Stein, and Michael K Sixt. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” Nature Immunology. Nature Publishing Group, 2018. https://doi.org/10.1038/s41590-018-0109-z.","mla":"Hons, Miroslav, et al. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” Nature Immunology, vol. 19, no. 6, Nature Publishing Group, 2018, pp. 606–16, doi:10.1038/s41590-018-0109-z.","short":"M. Hons, A. Kopf, R. Hauschild, A.F. Leithner, F.R. Gärtner, J. Abe, J. Renkawitz, J. Stein, M.K. Sixt, Nature Immunology 19 (2018) 606–616."},"publication":"Nature Immunology","page":"606 - 616","issue":"6","abstract":[{"text":"Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","_id":"15","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 19","title":"Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells","status":"public","month":"05","doi":"10.1038/s41590-018-0109-z","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"SSU"}],"external_id":{"isi":["000433041500026"],"pmid":["29777221"]},"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pubmed/29777221"}],"oa":1,"project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular navigation along spatial gradients","call_identifier":"H2020"},{"name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020","grant_number":"747687","_id":"260AA4E2-B435-11E9-9278-68D0E5697425"},{"name":"Molecular and system level view of immune cell migration","_id":"25A48D24-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1396-2014"},{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","call_identifier":"FP7","grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425"}],"isi":1,"quality_controlled":"1","ec_funded":1,"publist_id":"8040","related_material":{"record":[{"id":"6891","status":"public","relation":"dissertation_contains"}]},"author":[{"first_name":"Miroslav","last_name":"Hons","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav"},{"orcid":"0000-0002-2187-6656","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","last_name":"Kopf","first_name":"Aglaja","full_name":"Kopf, Aglaja"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert"},{"last_name":"Leithner","first_name":"Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F"},{"full_name":"Gärtner, Florian R","last_name":"Gärtner","first_name":"Florian R","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Abe, Jun","last_name":"Abe","first_name":"Jun"},{"id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369","first_name":"Jörg","last_name":"Renkawitz","full_name":"Renkawitz, Jörg"},{"first_name":"Jens","last_name":"Stein","full_name":"Stein, Jens"},{"full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"volume":19,"date_created":"2018-12-11T11:44:10Z","date_updated":"2024-03-28T23:30:40Z","pmid":1,"acknowledgement":"This work was funded by grants from the European Research Council (ERC StG 281556 and CoG 724373) and the Austrian Science Foundation (FWF) to M.S. and by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457 and CR23I3_156234 to J.V.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687, and J.R. was funded by an EMBO long-term fellowship (ALTF 1396-2014).","year":"2018","department":[{"_id":"MiSi"},{"_id":"Bio"}],"publisher":"Nature Publishing Group","publication_status":"published"},{"publist_id":"6221","publication_status":"published","department":[{"_id":"MiSi"}],"publisher":"Nature Publishing Group","year":"2016","pmid":1,"date_created":"2018-12-11T11:50:21Z","date_updated":"2021-01-12T06:48:33Z","volume":17,"author":[{"full_name":"Salzer, Elisabeth","first_name":"Elisabeth","last_name":"Salzer"},{"last_name":"Çaǧdaş","first_name":"Deniz","full_name":"Çaǧdaş, Deniz"},{"full_name":"Hons, Miroslav","last_name":"Hons","first_name":"Miroslav","orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Emily","last_name":"Mace","full_name":"Mace, Emily"},{"last_name":"Garncarz","first_name":"Wojciech","full_name":"Garncarz, Wojciech"},{"first_name":"Oezlem","last_name":"Petronczki","full_name":"Petronczki, Oezlem"},{"last_name":"Platzer","first_name":"René","full_name":"Platzer, René"},{"full_name":"Pfajfer, Laurène","first_name":"Laurène","last_name":"Pfajfer"},{"full_name":"Bilic, Ivan","last_name":"Bilic","first_name":"Ivan"},{"full_name":"Ban, Sol","first_name":"Sol","last_name":"Ban"},{"full_name":"Willmann, Katharina","last_name":"Willmann","first_name":"Katharina"},{"last_name":"Mukherjee","first_name":"Malini","full_name":"Mukherjee, Malini"},{"full_name":"Supper, Verena","first_name":"Verena","last_name":"Supper"},{"first_name":"Hsiangting","last_name":"Hsu","full_name":"Hsu, Hsiangting"},{"full_name":"Banerjee, Pinaki","last_name":"Banerjee","first_name":"Pinaki"},{"full_name":"Sinha, Papiya","last_name":"Sinha","first_name":"Papiya"},{"full_name":"Mcclanahan, Fabienne","first_name":"Fabienne","last_name":"Mcclanahan"},{"first_name":"Gerhard","last_name":"Zlabinger","full_name":"Zlabinger, Gerhard"},{"full_name":"Pickl, Winfried","last_name":"Pickl","first_name":"Winfried"},{"last_name":"Gribben","first_name":"John","full_name":"Gribben, John"},{"last_name":"Stockinger","first_name":"Hannes","full_name":"Stockinger, Hannes"},{"full_name":"Bennett, Keiryn","last_name":"Bennett","first_name":"Keiryn"},{"full_name":"Huppa, Johannes","last_name":"Huppa","first_name":"Johannes"},{"last_name":"Dupré","first_name":"Loï̈C","full_name":"Dupré, Loï̈C"},{"first_name":"Özden","last_name":"Sanal","full_name":"Sanal, Özden"},{"first_name":"Ulrich","last_name":"Jäger","full_name":"Jäger, Ulrich"},{"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":"Tezcan, Ilhan","last_name":"Tezcan","first_name":"Ilhan"},{"full_name":"Orange, Jordan","first_name":"Jordan","last_name":"Orange"},{"full_name":"Boztug, Kaan","last_name":"Boztug","first_name":"Kaan"}],"month":"12","quality_controlled":"1","external_id":{"pmid":["27776107"]},"oa":1,"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400263"}],"language":[{"iso":"eng"}],"doi":"10.1038/ni.3575","type":"journal_article","abstract":[{"lang":"eng","text":"RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. RASGRP1 deficiency was associated in T cells and B cells with decreased phosphorylation of the extracellular-signal-regulated serine kinase ERK, which was restored following expression of wild-type RASGRP1. RASGRP1 deficiency also resulted in defective proliferation, activation and motility of T cells and B cells. RASGRP1-deficient natural killer (NK) cells exhibited impaired cytotoxicity with defective granule convergence and actin accumulation. Interaction proteomics identified the dynein light chain DYNLL1 as interacting with RASGRP1, which links RASGRP1 to cytoskeletal dynamics. RASGRP1-deficient cells showed decreased activation of the GTPase RhoA. Treatment with lenalidomide increased RhoA activity and reversed the migration and activation defects of RASGRP1-deficient lymphocytes."}],"issue":"12","title":"RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics","status":"public","intvolume":" 17","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1137","oa_version":"Submitted Version","scopus_import":1,"day":"01","article_processing_charge":"No","article_type":"original","page":"1352 - 1360","publication":"Nature Immunology","citation":{"apa":"Salzer, E., Çaǧdaş, D., Hons, M., Mace, E., Garncarz, W., Petronczki, O., … Boztug, K. (2016). RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3575","ieee":"E. Salzer et al., “RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics,” Nature Immunology, vol. 17, no. 12. Nature Publishing Group, pp. 1352–1360, 2016.","ista":"Salzer E, Çaǧdaş D, Hons M, Mace E, Garncarz W, Petronczki O, Platzer R, Pfajfer L, Bilic I, Ban S, Willmann K, Mukherjee M, Supper V, Hsu H, Banerjee P, Sinha P, Mcclanahan F, Zlabinger G, Pickl W, Gribben J, Stockinger H, Bennett K, Huppa J, Dupré L, Sanal Ö, Jäger U, Sixt MK, Tezcan I, Orange J, Boztug K. 2016. RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nature Immunology. 17(12), 1352–1360.","ama":"Salzer E, Çaǧdaş D, Hons M, et al. RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nature Immunology. 2016;17(12):1352-1360. doi:10.1038/ni.3575","chicago":"Salzer, Elisabeth, Deniz Çaǧdaş, Miroslav Hons, Emily Mace, Wojciech Garncarz, Oezlem Petronczki, René Platzer, et al. “RASGRP1 Deficiency Causes Immunodeficiency with Impaired Cytoskeletal Dynamics.” Nature Immunology. Nature Publishing Group, 2016. https://doi.org/10.1038/ni.3575.","short":"E. Salzer, D. Çaǧdaş, M. Hons, E. Mace, W. Garncarz, O. Petronczki, R. Platzer, L. Pfajfer, I. Bilic, S. Ban, K. Willmann, M. Mukherjee, V. Supper, H. Hsu, P. Banerjee, P. Sinha, F. Mcclanahan, G. Zlabinger, W. Pickl, J. Gribben, H. Stockinger, K. Bennett, J. Huppa, L. Dupré, Ö. Sanal, U. Jäger, M.K. Sixt, I. Tezcan, J. Orange, K. Boztug, Nature Immunology 17 (2016) 1352–1360.","mla":"Salzer, Elisabeth, et al. “RASGRP1 Deficiency Causes Immunodeficiency with Impaired Cytoskeletal Dynamics.” Nature Immunology, vol. 17, no. 12, Nature Publishing Group, 2016, pp. 1352–60, doi:10.1038/ni.3575."},"date_published":"2016-12-01T00:00:00Z"},{"month":"01","day":"01","scopus_import":1,"date_published":"2016-01-01T00:00:00Z","doi":"10.1038/icb.2015.62","language":[{"iso":"eng"}],"publication":"Immunology and Cell Biology","citation":{"chicago":"Sreeramkumar, Vinatha, Miroslav Hons, Carmen Punzón, Jens Stein, David Sancho, Manuel Fresno Forcelledo, and Natalia Cuesta. “Efficient T-Cell Priming and Activation Requires Signaling through Prostaglandin E2 (EP) Receptors.” Immunology and Cell Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/icb.2015.62.","mla":"Sreeramkumar, Vinatha, et al. “Efficient T-Cell Priming and Activation Requires Signaling through Prostaglandin E2 (EP) Receptors.” Immunology and Cell Biology, vol. 94, no. 1, Nature Publishing Group, 2016, pp. 39–51, doi:10.1038/icb.2015.62.","short":"V. Sreeramkumar, M. Hons, C. Punzón, J. Stein, D. Sancho, M. Fresno Forcelledo, N. Cuesta, Immunology and Cell Biology 94 (2016) 39–51.","ista":"Sreeramkumar V, Hons M, Punzón C, Stein J, Sancho D, Fresno Forcelledo M, Cuesta N. 2016. Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. Immunology and Cell Biology. 94(1), 39–51.","ieee":"V. Sreeramkumar et al., “Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors,” Immunology and Cell Biology, vol. 94, no. 1. Nature Publishing Group, pp. 39–51, 2016.","apa":"Sreeramkumar, V., Hons, M., Punzón, C., Stein, J., Sancho, D., Fresno Forcelledo, M., & Cuesta, N. (2016). Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. Immunology and Cell Biology. Nature Publishing Group. https://doi.org/10.1038/icb.2015.62","ama":"Sreeramkumar V, Hons M, Punzón C, et al. Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. Immunology and Cell Biology. 2016;94(1):39-51. doi:10.1038/icb.2015.62"},"quality_controlled":"1","page":"39 - 51","abstract":[{"text":"Understanding the regulation of T-cell responses during inflammation and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. In this regard, prostaglandin E 2 (PGE 2) is mostly considered a myeloid-derived immunosuppressive molecule. We describe for the first time that T cells secrete PGE 2 during T-cell receptor stimulation. In addition, we show that autocrine PGE 2 signaling through EP receptors is essential for optimal CD4 + T-cell activation in vitro and in vivo, and for T helper 1 (Th1) and regulatory T cell differentiation. PGE 2 was found to provide additive co-stimulatory signaling through AKT activation. Intravital multiphoton microscopy showed that triggering EP receptors in T cells is also essential for the stability of T cell-dendritic cell (DC) interactions and Th-cell accumulation in draining lymph nodes (LNs) during inflammation. We further demonstrated that blocking EP receptors in T cells during the initial phase of collagen-induced arthritis in mice resulted in a reduction of clinical arthritis. This could be attributable to defective T-cell activation, accompanied by a decline in activated and interferon-γ-producing CD4 + Th1 cells in draining LNs. In conclusion, we prove that T lymphocytes secret picomolar concentrations of PGE 2, which in turn provide additive co-stimulatory signaling, enabling T cells to attain a favorable activation threshold. PGE 2 signaling in T cells is also required for maintaining long and stable interactions with DCs within LNs. Blockade of EP receptors in vivo impairs T-cell activation and development of T cell-mediated inflammatory responses. This may have implications in various pathophysiological settings.","lang":"eng"}],"publist_id":"6116","issue":"1","type":"journal_article","author":[{"full_name":"Sreeramkumar, Vinatha","last_name":"Sreeramkumar","first_name":"Vinatha"},{"last_name":"Hons","first_name":"Miroslav","orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","full_name":"Hons, Miroslav"},{"last_name":"Punzón","first_name":"Carmen","full_name":"Punzón, Carmen"},{"last_name":"Stein","first_name":"Jens","full_name":"Stein, Jens"},{"first_name":"David","last_name":"Sancho","full_name":"Sancho, David"},{"full_name":"Fresno Forcelledo, Manuel","last_name":"Fresno Forcelledo","first_name":"Manuel"},{"full_name":"Cuesta, Natalia","first_name":"Natalia","last_name":"Cuesta"}],"date_updated":"2021-01-12T06:49:09Z","date_created":"2018-12-11T11:50:46Z","volume":94,"oa_version":"None","acknowledgement":"This manuscript has been supported by grants SAF2007-61716 and S-SAL-0159/2006 awarded by the Spanish Ministry of Science and Education and the Community of Madrid to Dr M Fresno.","_id":"1217","year":"2016","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","status":"public","title":"Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors","publication_status":"published","department":[{"_id":"MiSi"}],"intvolume":" 94","publisher":"Nature Publishing Group"},{"type":"journal_article","publist_id":"5611","issue":"4","abstract":[{"text":"Stromal cells in the subcapsular sinus of the lymph node 'decide' which cells and molecules are allowed access to the deeper parenchyma. The glycoprotein PLVAP is a crucial component of this selector function.","lang":"eng"}],"_id":"1560","year":"2015","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Nature Publishing Group","department":[{"_id":"MiSi"}],"intvolume":" 16","status":"public","title":"The lymph node filter revealed","publication_status":"published","author":[{"first_name":"Miroslav","last_name":"Hons","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav"},{"full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"oa_version":"None","volume":16,"date_updated":"2021-01-12T06:51:36Z","date_created":"2018-12-11T11:52:43Z","scopus_import":1,"month":"03","day":"19","citation":{"ama":"Hons M, Sixt MK. The lymph node filter revealed. Nature Immunology. 2015;16(4):338-340. doi:10.1038/ni.3126","ieee":"M. Hons and M. K. Sixt, “The lymph node filter revealed,” Nature Immunology, vol. 16, no. 4. Nature Publishing Group, pp. 338–340, 2015.","apa":"Hons, M., & Sixt, M. K. (2015). The lymph node filter revealed. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3126","ista":"Hons M, Sixt MK. 2015. The lymph node filter revealed. Nature Immunology. 16(4), 338–340.","short":"M. Hons, M.K. Sixt, Nature Immunology 16 (2015) 338–340.","mla":"Hons, Miroslav, and Michael K. Sixt. “The Lymph Node Filter Revealed.” Nature Immunology, vol. 16, no. 4, Nature Publishing Group, 2015, pp. 338–40, doi:10.1038/ni.3126.","chicago":"Hons, Miroslav, and Michael K Sixt. “The Lymph Node Filter Revealed.” Nature Immunology. Nature Publishing Group, 2015. https://doi.org/10.1038/ni.3126."},"publication":"Nature Immunology","page":"338 - 340","quality_controlled":"1","date_published":"2015-03-19T00:00:00Z","doi":"10.1038/ni.3126","language":[{"iso":"eng"}]}]