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In the brain, fibroblasts are border-enriched cells whose dynamic molecular states and immune interactions after injury remain unclear\n                    <jats:sup>1<\/jats:sup>\n                    . Here we define the shared fibroblast\u2013immune response to brain injury. Early profibrotic myofibroblasts develop from pre-existing brain fibroblasts and infiltrate brain lesions, orchestrated by fibroblast TGF\u03b2 signalling, profibrotic macrophages and microglia, and perilesional glia. Myofibroblasts transition into several late fibroblast states, including lymphocyte-interactive fibroblasts. Interruption of the early myofibroblast state exacerbated sub-acute brain injury, tissue loss and secondary neuroinflammation, with increased mortality in the transient middle cerebral artery occlusion stroke model. Disruption of late lymphocyte\u2013fibroblast niches via selective loss of fibroblast chemokine CXCL12 led to late brain-specific innate inflammation and lymphocyte dispersal with increased IFN\u03b3 production. These data indicate the response to brain injury is coordinated by evolving temporal and spatial fibroblast states that limit functional tissue loss and chronic neuroinflammation.\n                  <\/jats:p>","DOI":"10.1038\/s41586-025-09449-2","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T15:03:47Z","timestamp":1756911827000},"page":"934-944","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Dynamic fibroblast\u2013immune interactions shape recovery after brain injury"],"prefix":"10.1038","volume":"646","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2486-1783","authenticated-orcid":false,"given":"Nathan A.","family":"Ewing-Crystal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-8518","authenticated-orcid":false,"given":"Nicholas M.","family":"Mroz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amara","family":"Larpthaveesarp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0471-8525","authenticated-orcid":false,"given":"Carlos O.","family":"Lizama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remy","family":"Pennington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8753-1469","authenticated-orcid":false,"given":"Pailin","family":"Chiaranunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason I.","family":"Dennis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony A.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Dean","family":"Merrill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia E.","family":"Caryotakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4864-7799","authenticated-orcid":false,"given":"Nikhita","family":"Kirthivasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3100-6934","authenticated-orcid":false,"given":"Tatsuya","family":"Tsukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Katewa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel L.","family":"McKinsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9017-8448","authenticated-orcid":false,"given":"Sophia C. 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D.S. is a founder of Pliant Therapeutics and has received research funding from Abbvie, Pfizer, and Pliant Therapeutics. D.S. serves on the Scientific Review Board for Genentech, and on the Inflammation Scientific Advisory Board for Amgen. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}