{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:16:27Z","timestamp":1792199787531,"version":"4.4.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"5","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AI138479"],"award-info":[{"award-number":["AI138479"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,1,30]]},"abstract":"<jats:p>\n                    Roughly one-half of mice with partial defects in two immune tolerance pathways (Aire\n                    <jats:sup>GW\/+<\/jats:sup>\n                    Lyn\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice) spontaneously develop severe damage to their retinas due to T cell reactivity to Aire-regulated interphotoreceptor retinoid\u2013binding protein (IRBP). Single-cell T cell receptor (TCR) sequencing of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells specific for a predominate epitope of IRBP showed a remarkable diversity of autoantigen-specific TCRs with greater clonal expansions in mice with disease. TCR transgenic mice made with an expanded IRBP-specific TCR (P2.U2) of intermediate affinity exhibited strong but incomplete negative selection of thymocytes. This negative selection was absent in IRBP\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice and greatly defective in Aire\n                    <jats:sup>GW\/+<\/jats:sup>\n                    mice. Most P2.U2\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice and all P2.U.2\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    Aire\n                    <jats:sup>GW\/+<\/jats:sup>\n                    mice rapidly developed inflammation of the retina and adjacent uvea (uveitis). Aire-dependent IRBP expression in the thymus also promoted Treg differentiation, but the niche for this fate determination was small, suggesting differences in antigen presentation leading to negative selection vs. thymic Treg differentiation and a stronger role for negative selection in preventing autoimmune disease in the retina.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2311487121","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T13:43:22Z","timestamp":1706017402000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5573-8991","authenticated-orcid":false,"given":"Mianmian","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6977-2728","authenticated-orcid":false,"given":"Yingyos","family":"Jittayasothorn","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892-1857"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5127-5328","authenticated-orcid":false,"given":"Douglas B.","family":"Gould","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143"},{"name":"Department of Anatomy, Cardiovascular Research Institute, Bakar Aging Research Institute, and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7140-7671","authenticated-orcid":false,"given":"Rachel R.","family":"Caspi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892-1857"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California, San Francisco, San Francisco, CA 94143"},{"name":"Department of Medicine, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony L.","family":"DeFranco","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 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Yin Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model. GEO database. https:\/\/www.ncbi.nlm.nih.gov\/geo. Deposited 24 October 2022."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2311487121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T13:43:31Z","timestamp":1706017411000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2311487121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,23]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,1,30]]}},"alternative-id":["10.1073\/pnas.2311487121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2311487121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,23]]},"assertion":[{"value":"2023-07-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2311487121"}}