--- _id: '9794' 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.' acknowledged_ssus: - _id: Bio - _id: EM-Fac - _id: PreCl - _id: LifeSc 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. article_processing_charge: No article_type: original author: - first_name: Frank P full_name: Assen, Frank P id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87 last_name: Assen orcid: 0000-0003-3470-6119 - first_name: Jun full_name: Abe, Jun last_name: Abe - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Tommaso full_name: Costanzo, Tommaso id: D93824F4-D9BA-11E9-BB12-F207E6697425 last_name: Costanzo orcid: 0000-0001-9732-3815 - first_name: Gabriel full_name: Krens, Gabriel id: 2B819732-F248-11E8-B48F-1D18A9856A87 last_name: Krens orcid: 0000-0003-4761-5996 - first_name: Markus full_name: Brown, Markus id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87 last_name: Brown - first_name: Burkhard full_name: Ludewig, Burkhard last_name: Ludewig - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 - first_name: Wolfgang full_name: Weninger, Wolfgang last_name: Weninger - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Sanjiv A. full_name: Luther, Sanjiv A. last_name: Luther - first_name: Jens V. full_name: Stein, Jens V. last_name: Stein - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-4561-241X 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 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 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. 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. 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. 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. date_created: 2021-08-06T09:09:11Z date_published: 2022-07-11T00:00:00Z date_updated: 2023-08-02T06:53:07Z day: '11' ddc: - '570' department: - _id: SiHi - _id: CaHe - _id: EdHa - _id: EM-Fac - _id: Bio - _id: MiSi doi: 10.1038/s41590-022-01257-4 ec_funded: 1 external_id: isi: - '000822975900002' file: - access_level: open_access checksum: 628e7b49809f22c75b428842efe70c68 content_type: application/pdf creator: dernst date_created: 2022-07-25T07:11:32Z date_updated: 2022-07-25T07:11:32Z file_id: '11642' file_name: 2022_NatureImmunology_Assen.pdf file_size: 11475325 relation: main_file success: 1 file_date_updated: 2022-07-25T07:11:32Z has_accepted_license: '1' intvolume: ' 23' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1246-1255 project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients publication: Nature Immunology publication_identifier: eissn: - 1529-2916 issn: - 1529-2908 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Multitier mechanics control stromal adaptations in swelling lymph nodes tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 23 year: '2022' ... --- _id: '10703' abstract: - lang: eng text: 'When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.' acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: EM-Fac 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. article_processing_charge: No article_type: original author: - first_name: Florian full_name: Gaertner, Florian last_name: Gaertner - first_name: Patricia full_name: Reis-Rodrigues, Patricia last_name: Reis-Rodrigues - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Juan full_name: Aguilera, Juan last_name: Aguilera - first_name: Michael full_name: Riedl, Michael id: 3BE60946-F248-11E8-B48F-1D18A9856A87 last_name: Riedl orcid: 0000-0003-4844-6311 - first_name: Alexander F full_name: Leithner, Alexander F id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87 last_name: Leithner orcid: 0000-0002-1073-744X - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Vanessa full_name: Zheden, Vanessa id: 39C5A68A-F248-11E8-B48F-1D18A9856A87 last_name: Zheden orcid: 0000-0002-9438-4783 - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: 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 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 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. 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. 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. 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. date_created: 2022-01-30T23:01:33Z date_published: 2022-01-10T00:00:00Z date_updated: 2024-03-28T23:30:23Z day: '10' ddc: - '570' department: - _id: MiSi - _id: EM-Fac - _id: NanoFab - _id: BjHo doi: 10.1016/j.devcel.2021.11.024 ec_funded: 1 external_id: isi: - '000768933800005' pmid: - '34919802' intvolume: ' 57' isi: 1 issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://www.sciencedirect.com/science/article/pii/S1534580721009497 month: '01' oa: 1 oa_version: Published Version page: 47-62.e9 pmid: 1 project: - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients publication: Developmental Cell publication_identifier: eissn: - 1878-1551 issn: - 1534-5807 publication_status: published publisher: Cell Press ; Elsevier quality_controlled: '1' related_material: record: - id: '12726' relation: dissertation_contains status: public - id: '14530' relation: dissertation_contains status: public - id: '12401' relation: dissertation_contains status: public scopus_import: '1' status: public title: WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 57 year: '2022' ... --- _id: '7885' abstract: - lang: eng 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. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: M-Shop 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. article_processing_charge: No article_type: original author: - first_name: Anne full_name: Reversat, Anne id: 35B76592-F248-11E8-B48F-1D18A9856A87 last_name: Reversat orcid: 0000-0003-0666-8928 - first_name: Florian R full_name: Gärtner, Florian R id: 397A88EE-F248-11E8-B48F-1D18A9856A87 last_name: Gärtner orcid: 0000-0001-6120-3723 - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Julian A full_name: Stopp, Julian A id: 489E3F00-F248-11E8-B48F-1D18A9856A87 last_name: Stopp - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Juan L full_name: Aguilera Servin, Juan L id: 2A67C376-F248-11E8-B48F-1D18A9856A87 last_name: Aguilera Servin orcid: 0000-0002-2862-8372 - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Matthieu full_name: Piel, Matthieu last_name: Piel - first_name: Andrew full_name: Callan-Jones, Andrew last_name: Callan-Jones - first_name: Raphael full_name: Voituriez, Raphael last_name: Voituriez - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: 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 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. 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. 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. 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. date_created: 2020-05-24T22:01:01Z date_published: 2020-06-25T00:00:00Z date_updated: 2024-03-28T23:30:24Z day: '25' department: - _id: NanoFab - _id: Bio - _id: MiSi doi: 10.1038/s41586-020-2283-z ec_funded: 1 external_id: isi: - '000532688300008' intvolume: ' 582' isi: 1 language: - iso: eng month: '06' oa_version: None page: 582–585 project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 26018E70-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29911 name: Mechanical adaptation of lamellipodial actin - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells publication: Nature publication_identifier: eissn: - '14764687' issn: - '00280836' publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/off-road-mode-enables-mobile-cells-to-move-freely/ record: - id: '14697' relation: dissertation_contains status: public - id: '12401' relation: dissertation_contains status: public scopus_import: '1' status: public title: Cellular locomotion using environmental topography type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 582 year: '2020' ... --- _id: '15' abstract: - lang: eng text: Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux. acknowledged_ssus: - _id: SSU acknowledgement: This work was funded by grants from the European Research Council (ERC StG 281556 and CoG 724373) and the Austrian Science Foundation (FWF) to M.S. and by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457 and CR23I3_156234 to J.V.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687, and J.R. was funded by an EMBO long-term fellowship (ALTF 1396-2014). article_processing_charge: No author: - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Alexander F full_name: Leithner, Alexander F id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87 last_name: Leithner orcid: 0000-0002-1073-744X - first_name: Florian R full_name: Gärtner, Florian R id: 397A88EE-F248-11E8-B48F-1D18A9856A87 last_name: Gärtner orcid: 0000-0001-6120-3723 - first_name: Jun full_name: Abe, Jun last_name: Abe - first_name: Jörg full_name: Renkawitz, Jörg id: 3F0587C8-F248-11E8-B48F-1D18A9856A87 last_name: Renkawitz orcid: 0000-0003-2856-3369 - first_name: Jens full_name: Stein, Jens last_name: Stein - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: 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 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 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. 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. 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. 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. date_created: 2018-12-11T11:44:10Z date_published: 2018-05-18T00:00:00Z date_updated: 2024-03-28T23:30:40Z day: '18' department: - _id: MiSi - _id: Bio doi: 10.1038/s41590-018-0109-z ec_funded: 1 external_id: isi: - '000433041500026' pmid: - '29777221' intvolume: ' 19' isi: 1 issue: '6' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pubmed/29777221 month: '05' oa: 1 oa_version: Published Version page: 606 - 616 pmid: 1 project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells - _id: 25A48D24-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1396-2014 name: Molecular and system level view of immune cell migration - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes (EU) publication: Nature Immunology publication_status: published publisher: Nature Publishing Group publist_id: '8040' quality_controlled: '1' related_material: record: - id: '6891' relation: dissertation_contains status: public scopus_import: '1' status: public title: Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 19 year: '2018' ... --- _id: '1137' 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. article_processing_charge: No article_type: original author: - first_name: Elisabeth full_name: Salzer, Elisabeth last_name: Salzer - first_name: Deniz full_name: Çaǧdaş, Deniz last_name: Çaǧdaş - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Emily full_name: Mace, Emily last_name: Mace - first_name: Wojciech full_name: Garncarz, Wojciech last_name: Garncarz - first_name: Oezlem full_name: Petronczki, Oezlem last_name: Petronczki - first_name: René full_name: Platzer, René last_name: Platzer - first_name: Laurène full_name: Pfajfer, Laurène last_name: Pfajfer - first_name: Ivan full_name: Bilic, Ivan last_name: Bilic - first_name: Sol full_name: Ban, Sol last_name: Ban - first_name: Katharina full_name: Willmann, Katharina last_name: Willmann - first_name: Malini full_name: Mukherjee, Malini last_name: Mukherjee - first_name: Verena full_name: Supper, Verena last_name: Supper - first_name: Hsiangting full_name: Hsu, Hsiangting last_name: Hsu - first_name: Pinaki full_name: Banerjee, Pinaki last_name: Banerjee - first_name: Papiya full_name: Sinha, Papiya last_name: Sinha - first_name: Fabienne full_name: Mcclanahan, Fabienne last_name: Mcclanahan - first_name: Gerhard full_name: Zlabinger, Gerhard last_name: Zlabinger - first_name: Winfried full_name: Pickl, Winfried last_name: Pickl - first_name: John full_name: Gribben, John last_name: Gribben - first_name: Hannes full_name: Stockinger, Hannes last_name: Stockinger - first_name: Keiryn full_name: Bennett, Keiryn last_name: Bennett - first_name: Johannes full_name: Huppa, Johannes last_name: Huppa - first_name: Loï̈C full_name: Dupré, Loï̈C last_name: Dupré - first_name: Özden full_name: Sanal, Özden last_name: Sanal - first_name: Ulrich full_name: Jäger, Ulrich last_name: Jäger - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 - first_name: Ilhan full_name: Tezcan, Ilhan last_name: Tezcan - first_name: Jordan full_name: Orange, Jordan last_name: Orange - first_name: Kaan full_name: Boztug, Kaan last_name: Boztug citation: 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 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 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. 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. 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. 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. date_created: 2018-12-11T11:50:21Z date_published: 2016-12-01T00:00:00Z date_updated: 2021-01-12T06:48:33Z day: '01' department: - _id: MiSi doi: 10.1038/ni.3575 external_id: pmid: - '27776107' intvolume: ' 17' issue: '12' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400263 month: '12' oa: 1 oa_version: Submitted Version page: 1352 - 1360 pmid: 1 publication: Nature Immunology publication_status: published publisher: Nature Publishing Group publist_id: '6221' quality_controlled: '1' scopus_import: 1 status: public title: RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 17 year: '2016' ... --- _id: '1217' abstract: - lang: eng 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. 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. author: - first_name: Vinatha full_name: Sreeramkumar, Vinatha last_name: Sreeramkumar - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Carmen full_name: Punzón, Carmen last_name: Punzón - first_name: Jens full_name: Stein, Jens last_name: Stein - first_name: David full_name: Sancho, David last_name: Sancho - first_name: Manuel full_name: Fresno Forcelledo, Manuel last_name: Fresno Forcelledo - first_name: Natalia full_name: Cuesta, Natalia last_name: Cuesta citation: 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 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 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. 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. 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. 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. date_created: 2018-12-11T11:50:46Z date_published: 2016-01-01T00:00:00Z date_updated: 2021-01-12T06:49:09Z day: '01' department: - _id: MiSi doi: 10.1038/icb.2015.62 intvolume: ' 94' issue: '1' language: - iso: eng month: '01' oa_version: None page: 39 - 51 publication: Immunology and Cell Biology publication_status: published publisher: Nature Publishing Group publist_id: '6116' quality_controlled: '1' scopus_import: 1 status: public title: Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 94 year: '2016' ... --- _id: '1560' abstract: - lang: eng 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. author: - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Hons M, Sixt MK. The lymph node filter revealed. Nature Immunology. 2015;16(4):338-340. doi:10.1038/ni.3126 apa: Hons, M., & Sixt, M. K. (2015). The lymph node filter revealed. Nature Immunology. Nature Publishing Group. https://doi.org/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. 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. ista: Hons M, Sixt MK. 2015. The lymph node filter revealed. Nature Immunology. 16(4), 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. short: M. Hons, M.K. Sixt, Nature Immunology 16 (2015) 338–340. date_created: 2018-12-11T11:52:43Z date_published: 2015-03-19T00:00:00Z date_updated: 2021-01-12T06:51:36Z day: '19' department: - _id: MiSi doi: 10.1038/ni.3126 intvolume: ' 16' issue: '4' language: - iso: eng month: '03' oa_version: None page: 338 - 340 publication: Nature Immunology publication_status: published publisher: Nature Publishing Group publist_id: '5611' quality_controlled: '1' scopus_import: 1 status: public title: The lymph node filter revealed type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 16 year: '2015' ...