[{"author":[{"full_name":"Gawish, Riem","first_name":"Riem","last_name":"Gawish"},{"full_name":"Varada, Rajagopal","last_name":"Varada","first_name":"Rajagopal"},{"full_name":"Deckert, Florian","first_name":"Florian","last_name":"Deckert"},{"full_name":"Hladik, Anastasiya","last_name":"Hladik","first_name":"Anastasiya"},{"full_name":"Steinbichl, Linda","last_name":"Steinbichl","first_name":"Linda"},{"last_name":"Cimatti","first_name":"Laura","full_name":"Cimatti, Laura"},{"full_name":"Milanovic, Katarina","last_name":"Milanovic","first_name":"Katarina"},{"last_name":"Jain","first_name":"Mamta","full_name":"Jain, Mamta"},{"full_name":"Torgasheva, Natalya","last_name":"Torgasheva","first_name":"Natalya"},{"last_name":"Tanzer","first_name":"Andrea","full_name":"Tanzer, Andrea"},{"full_name":"De Paepe, Kim","last_name":"De Paepe","first_name":"Kim"},{"first_name":"Tom","last_name":"Van De Wiele","full_name":"Van De Wiele, Tom"},{"full_name":"Hausmann, Bela","first_name":"Bela","last_name":"Hausmann"},{"full_name":"Lang, Michaela","last_name":"Lang","first_name":"Michaela"},{"first_name":"Martin","last_name":"Pechhacker","full_name":"Pechhacker, Martin"},{"first_name":"Nahla","last_name":"Ibrahim","full_name":"Ibrahim, Nahla"},{"last_name":"De Vries","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid"},{"full_name":"Brostjan, Christine","last_name":"Brostjan","first_name":"Christine"},{"orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Christoph","last_name":"Gasche","full_name":"Gasche, Christoph"},{"full_name":"Boon, Louis","first_name":"Louis","last_name":"Boon"},{"full_name":"Berry, David","last_name":"Berry","first_name":"David"},{"full_name":"Jantsch, Michael F.","first_name":"Michael F.","last_name":"Jantsch"},{"full_name":"Pereira, Fatima C.","first_name":"Fatima C.","last_name":"Pereira"},{"full_name":"Vesely, Cornelia","first_name":"Cornelia","last_name":"Vesely"}],"status":"public","publication":"Journal of Experimental Medicine","issue":"9","article_number":"e20240109","ddc":["570"],"volume":222,"acknowledgement":"Sequencing was performed by the Vienna BioCenter Core Facilities (Medical University of Vienna Core Facility) and the Biomedical Sequencing Facility at CeMM, Vienna. Cell sorting and flow cytometry were performed at the Core Facility Flow Cytometry and Imaging (Medical University of Vienna). We thank Jasmin Schwarz, Gudrun Kohl, Petra Pjevac, and Joana Seneca Silva from the Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna for assisting with amplicon and metagenomic sequencing, as well as repositing of sequencing data. We thank Sophia Derdak and Michael Schuster for initial data analysis, Robert Vilvoi and Stephan Hemm for animal handling, Marcel Kertesz for mouse genotyping, and Salwan Roumaia for next generation sequencing sample preparation. Treatment schemes and graphical abstracts were created with https://BioRender.com.\r\n\r\nThis work was supported by the Austrian Science Fund, grant number ZK 57-B28 to C. Vesely, R. Gawish, and F.C. Pereira; grant number V 1025-B to R. Gawish; grant number DOC32-B28 to R. Varada and M.F. Jantsch; and F8007 and P32678 to M.F. Jantsch. Open Access funding provided by Medical University of Vienna.","month":"09","file":[{"creator":"dernst","date_updated":"2025-12-30T09:00:04Z","date_created":"2025-12-30T09:00:04Z","access_level":"open_access","relation":"main_file","checksum":"708d61fb8cf1d83ee1e33ddcfde0857e","success":1,"file_name":"2025_JEM_Gawish.pdf","file_id":"20899","file_size":9349311,"content_type":"application/pdf"}],"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_published":"2025-09-01T00:00:00Z","has_accepted_license":"1","abstract":[{"text":"Patho-mechanistic origins of ulcerative colitis are still poorly understood. The actin cross-linker filamin A (FLNA) impacts cellular responses through interaction with cytosolic proteins. Posttranscriptional A-to-I editing generates two forms of FLNA: genome-encoded FLNAQ and FLNAR. FLNA is edited in colon fibroblasts, smooth muscle cells, and endothelial cells. We found that the FLNA editing status determines colitis severity. Editing was highest in healthy colons and reduced during murine and human colitis. Mice that exclusively express FLNAR were highly resistant to DSS-induced colitis, whereas fully FLNAQ animals developed severe inflammation. While the genetic induction of FLNA editing influenced transcriptional states of structural cells and microbiome composition, we found that FLNAR exerts protection specifically via myeloid cells, which are physiologically unedited. Introducing fixed FLNAR did not hamper cell migration but reduced macrophage inflammation and rendered neutrophils less prone to NETosis. Thus, loss of FLNA editing correlates with colitis severity, and targeted editing of myeloid cells serves as a novel therapeutic approach in intestinal inflammation.","lang":"eng"}],"citation":{"apa":"Gawish, R., Varada, R., Deckert, F., Hladik, A., Steinbichl, L., Cimatti, L., … Vesely, C. (2025). Filamin A editing in myeloid cells reduces intestinal inflammation and protects from colitis. <i>Journal of Experimental Medicine</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1084/jem.20240109\">https://doi.org/10.1084/jem.20240109</a>","short":"R. Gawish, R. Varada, F. Deckert, A. Hladik, L. Steinbichl, L. Cimatti, K. Milanovic, M. Jain, N. Torgasheva, A. Tanzer, K. De Paepe, T. Van De Wiele, B. Hausmann, M. Lang, M. Pechhacker, N. Ibrahim, I. de Vries, C. Brostjan, M.K. Sixt, C. Gasche, L. Boon, D. Berry, M.F. Jantsch, F.C. Pereira, C. Vesely, Journal of Experimental Medicine 222 (2025).","mla":"Gawish, Riem, et al. “Filamin A Editing in Myeloid Cells Reduces Intestinal Inflammation and Protects from Colitis.” <i>Journal of Experimental Medicine</i>, vol. 222, no. 9, e20240109, Rockefeller University Press, 2025, doi:<a href=\"https://doi.org/10.1084/jem.20240109\">10.1084/jem.20240109</a>.","ieee":"R. Gawish <i>et al.</i>, “Filamin A editing in myeloid cells reduces intestinal inflammation and protects from colitis,” <i>Journal of Experimental Medicine</i>, vol. 222, no. 9. Rockefeller University Press, 2025.","chicago":"Gawish, Riem, Rajagopal Varada, Florian Deckert, Anastasiya Hladik, Linda Steinbichl, Laura Cimatti, Katarina Milanovic, et al. “Filamin A Editing in Myeloid Cells Reduces Intestinal Inflammation and Protects from Colitis.” <i>Journal of Experimental Medicine</i>. Rockefeller University Press, 2025. <a href=\"https://doi.org/10.1084/jem.20240109\">https://doi.org/10.1084/jem.20240109</a>.","ama":"Gawish R, Varada R, Deckert F, et al. Filamin A editing in myeloid cells reduces intestinal inflammation and protects from colitis. <i>Journal of Experimental Medicine</i>. 2025;222(9). doi:<a href=\"https://doi.org/10.1084/jem.20240109\">10.1084/jem.20240109</a>","ista":"Gawish R, Varada R, Deckert F, Hladik A, Steinbichl L, Cimatti L, Milanovic K, Jain M, Torgasheva N, Tanzer A, De Paepe K, Van De Wiele T, Hausmann B, Lang M, Pechhacker M, Ibrahim N, de Vries I, Brostjan C, Sixt MK, Gasche C, Boon L, Berry D, Jantsch MF, Pereira FC, Vesely C. 2025. Filamin A editing in myeloid cells reduces intestinal inflammation and protects from colitis. Journal of Experimental Medicine. 222(9), e20240109."},"intvolume":"       222","date_updated":"2025-12-30T09:00:42Z","publisher":"Rockefeller University Press","year":"2025","OA_type":"hybrid","publication_status":"published","department":[{"_id":"MiSi"}],"type":"journal_article","oa":1,"day":"01","external_id":{"isi":["001502896900001"],"pmid":["40471139"]},"pmid":1,"title":"Filamin A editing in myeloid cells reduces intestinal inflammation and protects from colitis","article_processing_charge":"Yes (via OA deal)","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["1540-9538"],"issn":["0022-1007"]},"license":"https://creativecommons.org/licenses/by/4.0/","article_type":"original","language":[{"iso":"eng"}],"OA_place":"publisher","file_date_updated":"2025-12-30T09:00:04Z","doi":"10.1084/jem.20240109","scopus_import":"1","oa_version":"Published Version","_id":"19928","quality_controlled":"1","date_created":"2025-06-29T22:01:15Z","isi":1},{"doi":"10.1084/jem.20170896","_id":"6497","scopus_import":"1","oa_version":"Published Version","file_date_updated":"2020-07-14T12:47:32Z","language":[{"iso":"eng"}],"date_created":"2019-05-28T12:36:47Z","isi":1,"quality_controlled":"1","type":"journal_article","external_id":{"isi":["000440822900011"]},"day":"06","oa":1,"year":"2018","publication_status":"published","publisher":"Rockefeller University Press","department":[{"_id":"MiSi"}],"publication_identifier":{"issn":["0022-1007"],"eissn":["1540-9538"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","article_processing_charge":"No","title":"The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells","has_accepted_license":"1","citation":{"ista":"Moalli F, Ficht X, Germann P, Vladymyrov M, Stolp B, de Vries I, Lyck R, Balmer J, Fiocchi A, Kreutzfeldt M, Merkler D, Iannacone M, Ariga A, Stoffel MH, Sharpe J, Bähler M, Sixt MK, Diz-Muñoz A, Stein JV. 2018. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental Medicine. 2015(7), 1869–1890.","apa":"Moalli, F., Ficht, X., Germann, P., Vladymyrov, M., Stolp, B., de Vries, I., … Stein, J. V. (2018). The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. <i>The Journal of Experimental Medicine</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1084/jem.20170896\">https://doi.org/10.1084/jem.20170896</a>","ieee":"F. Moalli <i>et al.</i>, “The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells,” <i>The Journal of Experimental Medicine</i>, vol. 2015, no. 7. Rockefeller University Press, pp. 1869–1890, 2018.","short":"F. Moalli, X. Ficht, P. Germann, M. Vladymyrov, B. Stolp, I. de Vries, R. Lyck, J. Balmer, A. Fiocchi, M. Kreutzfeldt, D. Merkler, M. Iannacone, A. Ariga, M.H. Stoffel, J. Sharpe, M. Bähler, M.K. Sixt, A. Diz-Muñoz, J.V. Stein, The Journal of Experimental Medicine 2015 (2018) 1869–1890.","mla":"Moalli, Federica, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” <i>The Journal of Experimental Medicine</i>, vol. 2015, no. 7, Rockefeller University Press, 2018, pp. 1869–1890, doi:<a href=\"https://doi.org/10.1084/jem.20170896\">10.1084/jem.20170896</a>.","chicago":"Moalli, Federica, Xenia Ficht, Philipp Germann, Mykhailo Vladymyrov, Bettina Stolp, Ingrid de Vries, Ruth Lyck, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” <i>The Journal of Experimental Medicine</i>. Rockefeller University Press, 2018. <a href=\"https://doi.org/10.1084/jem.20170896\">https://doi.org/10.1084/jem.20170896</a>.","ama":"Moalli F, Ficht X, Germann P, et al. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. <i>The Journal of Experimental Medicine</i>. 2018;2015(7):1869–1890. doi:<a href=\"https://doi.org/10.1084/jem.20170896\">10.1084/jem.20170896</a>"},"abstract":[{"text":"T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b−/− CD8+ T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b−/− CD8+ T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b−/− CD8+ T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8+ T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue–resident T cell populations.","lang":"eng"}],"tmp":{"image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","short":"CC BY-NC-SA (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode"},"date_published":"2018-06-06T00:00:00Z","date_updated":"2023-09-19T14:52:08Z","intvolume":"      2015","issue":"7","publication":"The Journal of Experimental Medicine","status":"public","author":[{"first_name":"Federica","last_name":"Moalli","full_name":"Moalli, Federica"},{"full_name":"Ficht, Xenia","last_name":"Ficht","first_name":"Xenia"},{"full_name":"Germann, Philipp","last_name":"Germann","first_name":"Philipp"},{"full_name":"Vladymyrov, Mykhailo","last_name":"Vladymyrov","first_name":"Mykhailo"},{"last_name":"Stolp","first_name":"Bettina","full_name":"Stolp, Bettina"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"de Vries, Ingrid","last_name":"de Vries","first_name":"Ingrid"},{"last_name":"Lyck","first_name":"Ruth","full_name":"Lyck, Ruth"},{"last_name":"Balmer","first_name":"Jasmin","full_name":"Balmer, Jasmin"},{"full_name":"Fiocchi, Amleto","first_name":"Amleto","last_name":"Fiocchi"},{"full_name":"Kreutzfeldt, Mario","first_name":"Mario","last_name":"Kreutzfeldt"},{"first_name":"Doron","last_name":"Merkler","full_name":"Merkler, Doron"},{"last_name":"Iannacone","first_name":"Matteo","full_name":"Iannacone, Matteo"},{"last_name":"Ariga","first_name":"Akitaka","full_name":"Ariga, Akitaka"},{"full_name":"Stoffel, Michael H.","first_name":"Michael H.","last_name":"Stoffel"},{"full_name":"Sharpe, James","last_name":"Sharpe","first_name":"James"},{"full_name":"Bähler, Martin","last_name":"Bähler","first_name":"Martin"},{"orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Diz-Muñoz, Alba","last_name":"Diz-Muñoz","first_name":"Alba"},{"full_name":"Stein, Jens V.","last_name":"Stein","first_name":"Jens V."}],"page":"1869–1890","file":[{"date_created":"2019-05-28T12:40:05Z","access_level":"open_access","creator":"kschuh","date_updated":"2020-07-14T12:47:32Z","checksum":"86ae5331f9bfced9a6358a790a04bef4","relation":"main_file","file_id":"6498","file_name":"2018_rupress_Moalli.pdf","content_type":"application/pdf","file_size":3841660}],"volume":2015,"ddc":["570"],"month":"06"}]
