Extrathymic expression of Aire controls the induction of effective T(H)17 cell-mediated immune response to Candida albicans

0559553 - ÚMG 2023 RIV US eng J - Journal Article
Dobeš, J. - Ben-Nun, O. - Binyamin, A. - Stoler-Barak, L. - Oftedal, B.E. - Goldfarb, Y. - Kadouri, N. - Gruper, Y. - Givony, T. - Zalayat, I. - Kováčová, K. - Bohmova, H. - Valter, E. - Shulman, Z. - Filipp, Dominik - Husebye, E.S. - Abramson, J.
Extrathymic expression of Aire controls the induction of effective T(H)17 cell-mediated immune response to Candida albicans.
Nature Immunology. Roč. 23, č. 7 (2022), s. 1098-1108. ISSN 1529-2908. E-ISSN 1529-2916
R&D Projects: GA ČR(CZ) GA17-25365S
Institutional support: RVO:68378050
Keywords : Innate lymphoid-cells * Chronic mucocutaneous candidiasis * T-cells * Negative selection * Beta * Tolerance * Dificiency * Dectin-1 * Recognition * Autoimmune regulator
OECD category: Immunology
Impact factor: 30.5, year: 2022
Method of publishing: Limited access
https://www.nature.com/articles/s41590-022-01247-6

Patients with loss of function in the gene encoding the master regulator of central tolerance AIRE suffer from a devastating disorder called autoimmune polyendocrine syndrome type 1 (APS-1), characterized by a spectrum of autoimmune diseases and severe mucocutaneous candidiasis. Although the key mechanisms underlying the development of autoimmunity in patients with APS-1 are well established, the underlying cause of the increased susceptibility to Candida albicans infection remains less understood. Here, we show that Aire(+)MHCII(+) type 3 innate lymphoid cells (ILC3s) could sense, internalize and present C. albicans and had a critical role in the induction of Candida-specific T helper 17 (T(H)17) cell clones. Extrathymic Rorc-Cre-mediated deletion of Aire resulted in impaired generation of Candida-specific T(H)17 cells and subsequent overgrowth of C. albicans in the mucosal tissues. Collectively, our observations identify a previously unrecognized regulatory mechanism for effective defense responses against fungal infections.
Permanent Link: https://hdl.handle.net/11104/0332820