{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:41:51Z","timestamp":1794004911850,"version":"4.8.0"},"posted":{"date-parts":[[2025,10,2]]},"group-title":"Immunology","reference-count":246,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["DP1AR076959"],"award-info":[{"award-number":["DP1AR076959"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K99AG081564"],"award-info":[{"award-number":["K99AG081564"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Science Foundation","award":["DGE1746891"],"award-info":[{"award-number":["DGE1746891"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Immune-stromal crosstalk governs tissue fibrosis, which is marked by dysregulated extracellular matrix (ECM) production and aberrant vasculature. Here, we investigate how \u03b3\u03b4 T cell interactions with stromal cells shape fibrosis in the foreign body response. During the acute reaction, type-1 (\u03b3\u03b4IFN\u03b3) and type-17 (\u03b3\u03b417) effector subsets accumulated at the implant. While \u03b3\u03b4IFN\u03b3 decreased as fibrosis progressed, activated \u03b3\u03b417 persisted as dominant interleukin-17 producers. The \u03b3\u03b417 increased with aging and high-fat diet, both factors associated with chronic inflammation and fibrosis. Co-culture with \u03b3\u03b417 stimulated fibroblast expression of collagen genes and intercellular communication inference linked \u03b3\u03b4 T cell ligands to activation of ECM remodeling and vascular development programs in fibroblasts and endothelial cells. Finally, genetic deletion of \u03b3\u03b4 T cells altered expression of ECM components and increased vessel size within the fibrotic matrix. Altogether, our findings implicate \u03b3\u03b4 T cells in regulating stromal behavior to modulate composition and vascularity of fibrotic tissues.<\/jats:p>","DOI":"10.1101\/2025.09.30.679608","type":"posted-content","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:45:22Z","timestamp":1759452322000},"source":"Crossref","is-referenced-by-count":4,"title":["\u03b3\u03b417 T cell-stromal networks modulate matrix composition and vascularity in foreign body response"],"prefix":"10.64898","author":[{"given":"Anna","family":"Ruta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JiWon","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joscelyn C.","family":"Mej\u00edas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise F.","family":"Gray-Gaillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"David R.","family":"Maestas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen Hieu","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra N.","family":"Rindone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Cherry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Patatanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Haoning","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Amelung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina D.","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-2749","authenticated-orcid":false,"given":"Birgit","family":"Schilling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Gerecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elana J.","family":"Fertig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1526-7122","authenticated-orcid":false,"given":"Locke Davenport","family":"Huyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew M.","family":"Pardoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer H.","family":"Elisseeff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100617351281000_2025.09.30.679608v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00452-4"},{"key":"2025100617351281000_2025.09.30.679608v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0304-y"},{"key":"2025100617351281000_2025.09.30.679608v1.3","unstructured":"Vermijlen, D. , Gatti, D. , Kouzeli, A. , Rus, T. & Eberl, M . in Seminars in cell & developmental biology. 75\u201386 (Elsevier)."},{"key":"2025100617351281000_2025.09.30.679608v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.101"},{"key":"2025100617351281000_2025.09.30.679608v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0094-2"},{"key":"2025100617351281000_2025.09.30.679608v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2028-z"},{"key":"2025100617351281000_2025.09.30.679608v1.7","doi-asserted-by":"crossref","unstructured":"Douglas, A. et al. 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