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

Mohamed Benhammadi; Justine Mathé; Maude Dumont-Lagacé; Koichi S. Kobayashi; Louis Gaboury; Sylvie Brochu; Claude Perreault

doi:10.4049/jimmunol.2000225

Key Points

Thymic ECs express more MHC I molecules than extrathymic ECs.
Aire, Nlrc5, Stat1, and IFN-λ enhance constitutive MHC I expression in thymic ECs.

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.

Footnotes

This work was supported by Canadian Institutes of Health Research Grant FDN-148400 (to C.P.). The CD1d–α-GalCer tetramers were obtained through the National Institutes of Health Tetramer Core Facility.
The RNA-sequencing data reported in this article have been submitted to the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE144722.
The online version of this article contains supplemental material.