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Publication : IFN-λ Enhances Constitutive Expression of MHC Class I Molecules on Thymic Epithelial Cells.

First Author  Benhammadi M Year  2020
Journal  J Immunol Volume  205
Issue  5 Pages  1268-1280
PubMed ID  32690660 Mgi Jnum  J:294229
Mgi Id  MGI:6455105 Doi  10.4049/jimmunol.2000225
Citation  Benhammadi M, et al. (2020) IFN-lambda Enhances Constitutive Expression of MHC Class I Molecules on Thymic Epithelial Cells. J Immunol 205(5):1268-1280
abstractText  Regulation of MHC class I (MHC I) expression has been studied almost exclusively in hematolymphoid cells. 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-binding 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 (-/-) 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.
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