{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T01:36:19Z","timestamp":1762047379004,"version":"build-2065373602"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H06496","16K21731","18K19564","19H03699"],"award-info":[{"award-number":["16H06496","16K21731","18K19564","19H03699"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deficiency for AIRE\/Aire in both humans and mice results in the development of organ\u2010specific autoimmune disease. We tested whether augmented and\/or dysregulated AIRE\/Aire expression might be also prone to the breakdown of self\u2010tolerance. To define the effect of augmented Aire expression on the development of autoimmunity, antigen\u2010specific clonal deletion and production of clonotypic regulatory T cells (Tregs) in the thymus were examined using mice expressing two additional copies of Aire\u2009in a heterozygous state (3xAire\u2010knockin mice: 3xAire\u2010KI). We found that both clonal deletion of autoreactive T cells and production of clonotypic Tregs in the thymus from 3xAire\u2010KI were impaired in a T\u2010cell receptor\u2010transgenic system. Furthermore, 3xAire\u2010KI females showed higher scores of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein than wild\u2010type littermates, suggesting that augmented Aire expression exacerbates organ\u2010specific autoimmunity under disease\u2010prone conditions. In humans, we found that one patient with amyopathic dermatomyositis showed CD3<jats:sup>\u2013<\/jats:sup>CD19<jats:sup>\u2013<\/jats:sup> cells expressing AIRE in the peripheral blood before the treatment but not during the remission phase treated with immunosuppressive drugs. Thus, not only loss of function of AIRE\/Aire but also augmented and\/or dysregulated expression of AIRE\/Aire should be considered for the pathogenesis of organ\u2010specific autoimmunity. We suggest that further analyses should be pursued to establish a novel link between organ\u2010specific autoimmune disease and dysregulated AIRE expression in clinical settings.<\/jats:p>","DOI":"10.1111\/imcb.12546","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T20:24:45Z","timestamp":1647894285000},"page":"371-377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development of organ\u2010specific autoimmunity by dysregulated Aire expression"],"prefix":"10.1111","volume":"100","author":[{"given":"Hitoshi","family":"Nishijima","sequence":"first","affiliation":[{"name":"Division of Molecular Immunology Institute for Enzyme Research Tokushima University  Tokushima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizuki","family":"Sugita","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology Institute for Enzyme Research Tokushima University  Tokushima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsuka","family":"Umezawa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Kawano","sequence":"additional","affiliation":[{"name":"Department of Respiratory 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