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Medullary thymic epithelial cells (mTECs) play important roles in these selections, and their differentiation and maintenance depend on interaction with positively selected CD4+ single-positive cells. Therefore, migration and differentiation after positive selection must be coordinated to establish immune tolerance. However, the regulatory mechanisms of these processes are not fully understood. SATB1 is a genome organizer highly expressed in double-positive thymocytes, and SATB1 deletion causes various defects in T-cell development, including impaired positive and negative selection and tTreg differentiation. Here, we show that SATB1 is critical for temporally coordinated thymocyte trafficking after positive selection in mice. Satb1 knockout (\u0394Satb1) led to precocious thymic egress caused by augmented S1pr1 upregulation in positively selected thymocytes, accompanied by lower induction of Ccr7, Tnfsf11, and Cd40lg. Altered thymocyte trafficking and functionality affected the differentiation of mTECs and, in turn, tTreg differentiation. Thus, SATB1 is required to establish immune tolerance, at least in part, by ensuring timely thymic egress and mTEC differentiation.<\/jats:p>","DOI":"10.4049\/jimmunol.2200572","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T10:27:40Z","timestamp":1685528860000},"page":"209-218","source":"Crossref","is-referenced-by-count":8,"title":["Crucial Roles of SATB1 in Regulation of Thymocyte Migration after Positive Selection"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6440-5566","authenticated-orcid":false,"given":"Taku","family":"Naito","sequence":"first","affiliation":[{"name":"Department of Molecular Immunology, Toho University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marii","family":"Ise","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Toho University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9278-7677","authenticated-orcid":false,"given":"Yuriko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Toho University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terumi","family":"Kohwi-Shigematsu","sequence":"additional","affiliation":[{"name":"Department of Orofacial Science, University of California , San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-8804","authenticated-orcid":false,"given":"Motonari","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Toho University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"2025020406021388900_r1","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/S0140-6736(61)90693-6","article-title":"Immunological function of the thymus","volume":"278","author":"Miller","year":"1961","journal-title":"Lancet"},{"key":"2025020406021388900_r2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nri798","article-title":"T-cell development and the CD4-CD8 lineage decision","volume":"2","author":"Germain","year":"2002","journal-title":"Nat. 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