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We identified a counterregulatory network between the homologous transcription factors ZEB1 and ZEB2 and the miR-200 microRNA family, which modulates effector CD8+ T cell fates. Unexpectedly, Zeb1 and Zeb2 had reciprocal expression patterns and were functionally uncoupled in CD8+ T cells. ZEB2 promoted terminal differentiation, whereas ZEB1 was critical for memory T cell survival and function. Interestingly, the transforming growth factor \u03b2 (TGF-\u03b2) and miR-200 family members, which counterregulate the coordinated expression of Zeb1 and Zeb2 during the epithelial-to-mesenchymal transition, inversely regulated Zeb1 and Zeb2 expression in CD8+ T cells. TGF-\u03b2 induced and sustained Zeb1 expression in maturing memory CD8+ T cells. Meanwhile, both TGF-\u03b2 and miR-200 family members selectively inhibited Zeb2. Additionally, the miR-200 family was necessary for optimal memory CD8+ T cell formation. These data outline a previously unknown genetic pathway in CD8+ T cells that controls effector and memory cell fate decisions.<\/jats:p>","DOI":"10.1084\/jem.20171352","type":"journal-article","created":{"date-parts":[[2018,2,15]],"date-time":"2018-02-15T09:55:17Z","timestamp":1518688517000},"page":"1153-1168","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":159,"title":["ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fates"],"prefix":"10.1084","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6187-5431","authenticated-orcid":true,"given":"Tianxia","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia X.","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6868-7193","authenticated-orcid":true,"given":"Robert A.","family":"Amezquita","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Laidlaw","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jijun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Genetics and Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Henao-Mejia","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-0778","authenticated-orcid":true,"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 1"},{"name":"Howard Hughes Medical Institute, Yale University, New Haven, CT 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3339-8698","authenticated-orcid":true,"given":"Susan M.","family":"Kaech","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,2,15]]},"reference":[{"key":"2023072604321731100_bib1","doi-asserted-by":"publisher","first-page":"4988","DOI":"10.4049\/jimmunol.1002042","article-title":"Cutting edge: The transcription factor eomesodermin enables CD8+ T cells to compete for the memory cell niche","volume":"185","author":"Banerjee","year":"2010","journal-title":"J. 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