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We report that thymic epithelial cells (TECs), particularly the medullary TECs, constitutively express up to 100-fold more cell surface MHC I proteins than epithelial cells (ECs) from the skin, colon, and lung. Differential abundance of cell surface MHC I in primary ECs is regulated via transcription of MHC I and of genes implicated in the generation of MHC I\u2013binding peptides. Superior MHC I expression in TECs is unaffected by deletion of Ifnar1 or Ifngr1, but is lessened by deletion of Aire, Ifnlr1, Stat1, or Nlrc5, and is driven mainly by type III IFN produced by medullary TECs. Ifnlr1\u2212\/\u2212 mice show impaired negative selection of CD8 thymocytes and, at 9 mo of age, present autoimmune manifestations. Our study shows unanticipated variation in MHC I expression by ECs from various sites and provides compelling evidence that superior expression of MHC I in TECs is crucial for proper thymocyte education.<\/jats:p>","DOI":"10.4049\/jimmunol.2000225","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T16:23:03Z","timestamp":1595262183000},"page":"1268-1280","source":"Crossref","is-referenced-by-count":56,"title":["IFN-\u03bb Enhances Constitutive Expression of MHC Class I Molecules on Thymic Epithelial Cells"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-7734","authenticated-orcid":false,"given":"Mohamed","family":"Benhammadi","sequence":"first","affiliation":[{"name":"Institute for Research in Immunology and Cancer, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Math\u00e9","sequence":"additional","affiliation":[{"name":"Institute for Research in Immunology and Cancer, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maude","family":"Dumont-Lagac\u00e9","sequence":"additional","affiliation":[{"name":"Institute for Research in Immunology and Cancer, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi S","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center , College Station, TX 77843"},{"name":"Department of Immunology, Hokkaido University Graduate School of Medicine , Sapporo, Hokkaido 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7093-8139","authenticated-orcid":false,"given":"Louis","family":"Gaboury","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, University of Montreal , Montreal, Quebec H3T 1J4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4665-0936","authenticated-orcid":false,"given":"Sylvie","family":"Brochu","sequence":"additional","affiliation":[{"name":"Institute for Research in Immunology and Cancer, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9453-7383","authenticated-orcid":false,"given":"Claude","family":"Perreault","sequence":"additional","affiliation":[{"name":"Institute for Research in Immunology and Cancer, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec H3C 3J7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"2025030417504847700_r1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41577-018-0007-5","article-title":"Understanding the drivers of MHC restriction of T cell receptors","volume":"18","author":"La Gruta","year":"2018","journal-title":"Nat. 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