1. IFN-λ Enhances Constitutive Expression of MHC Class I Molecules on Thymic Epithelial Cells.
- Author
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Benhammadi M, Mathé J, Dumont-Lagacé M, Kobayashi KS, Gaboury L, Brochu S, and Perreault C
- Subjects
- Animals, CD8-Positive T-Lymphocytes immunology, Female, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Thymocytes immunology, Interferon Lambda, Epithelial Cells immunology, Histocompatibility Antigens Class I immunology, Interferons immunology, Receptors, Interferon immunology, Thymus Gland immunology
- Abstract
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., (Copyright © 2020 by The American Association of Immunologists, Inc.)- Published
- 2020
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