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Mohamed Benhammadi, Maude Dumont-Lagacé, Justine Mathé, Koichi S Kobayashi, Louis Gaboury, Sylvie Brochu, Claude Perreault, INF-λ enhances expression of MHC class I molecules on thymic epithelial, The Journal of Immunology, Volume 206, Issue 1_Supplement, May 2021, Page 93.13, https://doi.org/10.4049/jimmunol.206.Supp.93.13
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Abstract
The major histocompatibility complex class I (MHC-I) molecules is a cell surface glycoprotein involved in the presentation of endogenously derived peptides, to the TCR of CD8 T cells. Moreover, several vital processes specifically depend on the interaction between TCR and the MHC-I presented by the epithelial cells (ECs). However, the regulation of the MHC-I expression has been studied almost exclusively in hematolymphoid cells and very little is known about this process in ECs. In the present work, we performed a deep analysis of MHC-I expression in primary ECs freshly harvested from the thymus, skin, gut, and lung.
Our flow cytometry analysis showed that the abundance of cell surface MHC-I was overall 10- to 100-fold greater in thymic ECs (TECs) than in extrathymic EC types. Our transcriptomic analysis revealed a dominant role of IFN signalling in the differential MHC-I expression found in TECs vs. extrathymic ECs. In fact, 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 IFN-λ produced by TECs. Moreover, Ifnlr1−/− mice showed impaired negative selection of CD8 thymocytes, and at 9 months of age, present autoimmune manifestations.
In conclusion, our study opens the door to a new level of understanding of MHC-I regulation in ECs and will pave the way for a more detailed exploration of the impact of IFN-λ signaling in thymic functions.
