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The mechanism by which an activated, inflammatory fibroblast acquires tissue destructive behaviors is unknown. Here, we describe ARID5B as a transcription factor that directs inflammatory fibroblasts to become migratory and invasive. Upon upregulation in inflammatory fibroblasts, ARID5B binds to histone editors and localizes to both inflammatory and invasive gene loci, epigenetically repressing pro-inflammatory genes while enhancing expression of pro-invasive genes. Likewise, fibroblast-specific ARID5B overexpression\n                  <jats:italic>in vivo<\/jats:italic>\n                  drives an inflammatory-to-erosive shift in arthritis pathology. Our findings highlight ARID5B as a maladaptive brake on inflammatory fibroblast activation that endows fibroblasts with pathologic invasive properties, thus mechanistically linking fibroblast-driven tissue inflammation to tissue damage. These insights into the regulation of inflammatory and invasive fibroblast pathology may inform successful therapeutic targeting of fibroblasts in inflammatory diseases.\n                <\/jats:p>","DOI":"10.64898\/2026.08.04.742822","type":"posted-content","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T01:20:18Z","timestamp":1786411218000},"source":"Crossref","is-referenced-by-count":0,"title":["ARID5B drives an inflammatory-to-destructive shift in pathologic fibroblast behavior"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9709-3121","authenticated-orcid":false,"given":"Angela E.","family":"Zou","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School; Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suppawat","family":"Kongthong","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School; Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald F.M.","family":"Watts","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School; Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra L.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School; Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison L.","family":"Fairfield","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School; Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa A.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School; Boston, MA, USA"},{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA and Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School; Boston, MA, USA"},{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA and Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081120352672000_2026.08.04.742822v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00540-z"},{"key":"2026081120352672000_2026.08.04.742822v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.06.024"},{"key":"2026081120352672000_2026.08.04.742822v1.3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092642"},{"key":"2026081120352672000_2026.08.04.742822v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0322-7"},{"key":"2026081120352672000_2026.08.04.742822v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01789-0"},{"key":"2026081120352672000_2026.08.04.742822v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nature25501"},{"key":"2026081120352672000_2026.08.04.742822v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01520-5"},{"key":"2026081120352672000_2026.08.04.742822v1.8","doi-asserted-by":"crossref","unstructured":"Krishnamurty, A.T. et al. 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