IFN-λ Enhances Constitutive Expression of MHC Class I Molecules on Thymic Epithelial Cells
| Autor: | Mohamed Benhammadi, Claude Perreault, Justine Mathé, Louis Gaboury, Koichi Kobayashi, Maude Dumont-Lagacé, Sylvie Brochu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Immunology Cell chemical and pharmacologic phenomena Thymus Gland CD8-Positive T-Lymphocytes Major histocompatibility complex Interferon Lambda 03 medical and health sciences Negative selection Mice 0302 clinical medicine NLRC5 MHC class I medicine Immunology and Allergy Animals STAT1 Receptors Interferon Mice Inbred BALB C Thymocytes biology Histocompatibility Antigens Class I Epithelial Cells Cell biology Mice Inbred C57BL Thymocyte medicine.anatomical_structure biology.protein Female Interferons CD8 030215 immunology |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 205(5) |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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