{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:28:11Z","timestamp":1789079291216,"version":"build-2803163510"},"reference-count":85,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"88","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,10,27]]},"abstract":"<jats:p>\n            Mutations in the gene encoding the zinc-finger transcription factor Ikaros (\n            <jats:italic>IKZF1<\/jats:italic>\n            ) are found in patients with immunodeficiency, leukemia, and autoimmunity. Although Ikaros has a well-established function in modulating gene expression programs important for hematopoietic development, its role in other cell types is less well defined. Here, we uncover functions for Ikaros in thymic epithelial lineage development in mice and show that\n            <jats:italic>Ikzf1<\/jats:italic>\n            expression in medullary thymic epithelial cells (mTECs) is required for both autoimmune regulator\u2013positive (Aire\n            <jats:sup>+<\/jats:sup>\n            ) mTEC development and tissue-specific antigen (TSA) gene expression. Accordingly, TEC-specific deletion of\n            <jats:italic>Ikzf1<\/jats:italic>\n            in mice results in a profound decrease in Aire\n            <jats:sup>+<\/jats:sup>\n            mTECs, a global loss of TSA gene expression, and the development of autoimmunity. Moreover, Ikaros shapes thymic mimetic cell diversity, and its deletion results in a marked expansion of thymic tuft cells and muscle-like mTECs and a loss of other Aire-dependent mimetic populations. Single-cell analysis reveals that Ikaros modulates core transcriptional programs in TECs that correlate with the observed cellular changes. Our findings highlight a previously undescribed role for Ikaros in regulating epithelial lineage development and function and suggest that failed thymic central tolerance could contribute to the autoimmunity seen in humans with\n            <jats:italic>IKZF1<\/jats:italic>\n            mutations.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.abq3109","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T17:59:36Z","timestamp":1698429576000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":14,"title":["Ikaros is a principal regulator of Aire\n            <sup>+<\/sup>\n            mTEC homeostasis, thymic mimetic cell diversity, and central tolerance"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7338-3877","authenticated-orcid":true,"given":"Jun Hyung","family":"Sin","sequence":"first","affiliation":[{"name":"Biomedical Sciences Graduate Program, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."},{"name":"Department of Pediatrics, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0979-3903","authenticated-orcid":true,"given":"Juliana","family":"Sucharov","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5666-1217","authenticated-orcid":true,"given":"Sujit","family":"Kashyap","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1985-3404","authenticated-orcid":true,"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."},{"name":"10x Genomics, Pleasanton, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Proekt","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6546-3725","authenticated-orcid":true,"given":"Xian","family":"Liu","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."},{"name":"Diabetes Center, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4506-6268","authenticated-orcid":true,"given":"Audrey V.","family":"Parent","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2813-6175","authenticated-orcid":true,"given":"Alexander","family":"Gupta","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."},{"name":"Department of Surgery, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Kastner","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), INSERM U 1258, CNRS UMR 7104, Universit\u00e9 de Strasbourg, 67404 Illkirch, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Chan","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), INSERM U 1258, CNRS UMR 7104, Universit\u00e9 de Strasbourg, 67404 Illkirch, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3470-9520","authenticated-orcid":true,"given":"James M.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."},{"name":"Diabetes Center, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."},{"name":"Department of Surgery, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2477-0670","authenticated-orcid":true,"given":"Vasilis","family":"Ntranos","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."},{"name":"Diabetes Center, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1291-0074","authenticated-orcid":true,"given":"Corey N.","family":"Miller","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California San\u00a0Francisco, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3093-4758","authenticated-orcid":true,"given":"Mark S.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate 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