{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:13:12Z","timestamp":1790082792633,"version":"4.0.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    In order to address the question of how genetic compromises in multiple immune tolerance mechanisms might confer susceptibility to autoimmune disease development, we have bred together a partial loss of function in Aire, which is important for central tolerance of T cells, with a deficiency of the intracellular protein tyrosine kinase Lyn, which is important for function of inhibitory receptors of dendritic cells, B lymphocytes, and myeloid cells. These\n                    <jats:italic>\n                      Aire\n                      <jats:sup>GW\/+<\/jats:sup>\n                      Lyn\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mice spontaneously develop severe eye autoimmunity, characterized by retinal destruction and damage to the surrounding uvea, referred to as retinitis or uveoretinitis. Remarkably, this disease develops between 6 and 9 weeks of age in 50% of the mice, whereas the remaining 50% never develop disease. This disease is completely dependent on interphotoreceptor retinoid-binding protein (IRBP), a protein expressed primarily in retinal photoreceptor cells and, in the thymus under the control of Aire. Moreover, the dominant T cell epitope of this protein has been identified, and the corresponding autoreactive T cells can be characterized using peptide\/MHC tetramers and flow cytometry. In this review, we summarize findings to date with this recently developed mouse model of spontaneously developing organ-specific autoimmune disease. In addition, we discuss conclusions from these findings that provide mechanistic insights into disease initiation, discuss similarities and differences to other mouse models of uveoretinitis, and discuss the complementary nature of what likely can be learned with this model compared to the highly studied NOD mouse model of autoimmune diabetes.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1923275","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:48:42Z","timestamp":1790081322000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spontaneous organ-specific eye autoimmune disease resulting from two engineered gene mutations compromising immune tolerance"],"prefix":"10.3389","volume":"17","author":[{"given":"Mianmian","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California, San Francisco","place":["San Francisco, CA, United States"]},{"name":"Department of Medicine, UCSF","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford A.","family":"Lowell","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California","place":["San Francisco, San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony L.","family":"DeFranco","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco","place":["San Francisco, CA, United 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