{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T02:02:21Z","timestamp":1770775341366,"version":"3.50.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>T cell factor 1 (TCF-1) is expressed in both developing and mature T cells and has been shown to restrain mature T cell\u2013mediated Th17 responses by inhibiting IL-17 expression. However, it is not clear when TCF-1 is required in vivo to restrain the magnitude of peripheral Th17 responses and what the molecular mechanisms responsible for TCF-1\u2013regulated IL-17 gene expression are. In this study, we showed that conditional deletion of TCF-1 at the early but not later CD4+CD8+ double-positive stage in mice enhanced Th17 differentiation and aggravated experimental autoimmune encephalomyelitis, which correlates with abnormally high IL-17 expression. Expression of TCF-1 in TCF-1\u2013deficient thymocytes but not TCF-1\u2013deficient Th17 cells inhibited IL-17 expression. TCF-1 binds to IL-17 promoter regions, and deletion of two TCF-1 binding sites relieves TCF-1\u2013mediated inhibition of IL-17 promoter activity. Lastly, wild-type TCF-1, but not a TCF-1 mutant that has no intrinsic histone deacetylase activity, was able to inhibit IL-17 expression in TCF-1 deficient mouse thymocytes. Thus, our study demonstrates the requirement of TCF-1 in vivo at stages earlier than double-positive cells to restrain peripheral Th17 immunity by directly binding and inhibiting IL-17 promoter in its intrinsic histone deacetylase\u2013dependent manner.<\/jats:p>","DOI":"10.4049\/jimmunol.1800193","type":"journal-article","created":{"date-parts":[[2018,4,9]],"date-time":"2018-04-09T14:55:21Z","timestamp":1523285721000},"page":"3397-3406","source":"Crossref","is-referenced-by-count":22,"title":["TCF-1 Inhibits IL-17 Gene Expression To Restrain Th17 Immunity in a Stage-Specific Manner"],"prefix":"10.1093","volume":"200","author":[{"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Molecular Immunology, Beckman Research Institute of the City of Hope , Duarte, CA 91010"},{"name":"Irell and Manella Graduate School of Biological Sciences at City of Hope , Duarte, CA 91010"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiheng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Beckman Research Institute of the City of Hope , Duarte, CA 91010"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subha","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Beckman Research Institute of the City of Hope , Duarte, CA 91010"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Beckman Research Institute of the City of Hope , Duarte, CA 91010"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5686-9253","authenticated-orcid":false,"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute , Tianjin 300052,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuoming","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Beckman Research Institute of the City of Hope , Duarte, CA 91010"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"2025030610150730300_r1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1146\/annurev.iy.13.040195.000521","article-title":"Positive selection of thymocytes","volume":"13","author":"Jameson","year":"1995","journal-title":"Annu. 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