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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Mohamed BenhammadiClaude Perreault

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.

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Citations

Sep 17, 2020·Cancers·Anca ApavaloaeiClaude Perreault
Mar 7, 2021·International Journal of Molecular Sciences·Akhil ShuklaSubburaj Ilangumaran
Apr 29, 2021·Nature Reviews. Rheumatology·Rishi R GoelMariana J Kaplan
May 13, 2021·Nature Reviews. Clinical Oncology·Laurence ZitvogelGuido Kroemer
May 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yiwen ZhangHui Zhang

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