{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:42:51Z","timestamp":1790941371623,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,11,25]]},"abstract":"<jats:p>\n                    Autoimmune polyendocrine syndrome type I (APS I) results in multiple endocrine organ destruction and is caused by mutations in the autoimmune regulator gene (\n                    <jats:italic>AIRE<\/jats:italic>\n                    ). APS I is characterized by circulating tissue-specific autoantibodies, and the presence of these antibodies is often predictive of organ destruction. The importance of AIRE in ensuring central tolerance by regulating the negative selection of autoreactive T cells has been shown clearly. However, in\n                    <jats:italic>Aire<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice the phenotype (i.e., autoantibodies, liver infiltrates of B cells, splenomegaly, and marginal zone B-cell lymphoma) is predominantly B-cell mediated, suggesting an exaggerated activation of B cells. We have studied T-cell-independent B-cell responses in the absence of\n                    <jats:italic>AIRE<\/jats:italic>\n                    and found that\n                    <jats:italic>Aire<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice have an increased response against T-cell-independent type II antigens. We linked this exaggerated response to the elevated serum levels of the B-cell-activating factor of the TNF family (BAFF) that were found both in APS I patients and in\n                    <jats:italic>Aire<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Transfer of\n                    <jats:italic>Aire<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    bone marrow into irradiated nude mice resulted in increased percentage of BAFF-expressing antigen-presenting cells compared with wt bone marrow, suggesting a T-cell-independent mechanism behind our findings. Furthermore,\n                    <jats:italic>in<\/jats:italic>\n                    vitro experiments showed that AIRE-deficient murine bone marrow-derived dendritic cells produced significantly more BAFF than wt cells when stimulated with IFN-\u03b3 but not when stimulated with IL-10. Our results suggest a cell-intrinsic role for AIRE in peripheral dendritic cells by regulating IFN-\u03b3-receptor signaling and point toward complementary mechanisms by which AIRE is involved in maintaining tolerance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0808205105","type":"journal-article","created":{"date-parts":[[2008,11,14]],"date-time":"2008-11-14T20:54:26Z","timestamp":1226696066000},"page":"18466-18471","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["AIRE regulates T-cell-independent B-cell responses through BAFF"],"prefix":"10.1073","volume":"105","author":[{"given":"Emma","family":"Lindh","sequence":"first","affiliation":[{"name":"Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Lind","sequence":"additional","affiliation":[{"name":"Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"Lindmark","sequence":"additional","affiliation":[{"name":"Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe","family":"H\u00e4ssler","sequence":"additional","affiliation":[{"name":"Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Perheentupa","sequence":"additional","affiliation":[{"name":"Hospital for Children and Adolescents, Helsinki University Hospital, 00029, Helsinki, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Peltonen","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics, National Public Health Institute, 00300, Helsinki, Finland; and"},{"name":"Department of Medical Genetics, University of Helsinki, 00251, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Winqvist","sequence":"additional","affiliation":[{"name":"Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael C. 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