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This study aimed to elucidate the mechanisms by which TRIM21 autoimmunity drives ILD using an in vivo model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A murine model of TRIM21 autoimmunity was established by immunizing mice with full-length recombinant TRIM21 protein. Lung immune infiltration and antibody production were assessed. To mimic viral triggers, mice received poly(I:C). Immune cell subsets and transcriptional changes were analyzed using flow cytometry, RNA sequencing, and immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TRIM21 immunization induced systemic autoantibody production and B cell activation, which were associated with selective pulmonary inflammation marked by IgG deposition. Upon poly(I:C) challenge, lung inflammation was markedly exacerbated, with increased infiltration of CD8\n                      <jats:sup>+<\/jats:sup>\n                      cells and CD11b\n                      <jats:sup>+<\/jats:sup>\n                      myeloid cells and enrichment of chemokine signaling pathways. RNA sequencing identified Ccl6 as a top upregulated gene, and its protein expression was spatially validated in inflamed lung tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings support a pathogenic role for anti-Ro52\/TRIM21 autoimmunity in CTD-associated ILD. Our in vivo model reveals a lung-predominant inflammatory response associated with CD8\n                      <jats:sup>+<\/jats:sup>\n                      cell that is amplified by viral mimicry and accompanied by CCL6 signaling, offering mechanistic insight and potential therapeutic targets in anti-Ro52 positive ILD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-026-03850-6","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:39:18Z","timestamp":1782437958000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tripartite motif containing 21 autoimmunity primes CD8+ cell\u2013mediated lung inflammation: an in vivo model of interstitial lung disease pathogenesis"],"prefix":"10.1186","volume":"28","author":[{"given":"Yulu","family":"Qiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"issue":"1","key":"3850_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/s41572-021-00321-x","volume":"7","author":"IE Lundberg","year":"2021","unstructured":"Lundberg IE, Fujimoto M, Vencovsky J, et al. 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