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 (TH17) cell clones. Extrathymic Rorc-Cre-mediated deletion of Aire resulted in impaired generation of Candida-specific TH17 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.

Department of Cell Biology Faculty of Science Charles University Prague Czech Republic

Department of Clinical Science University of Bergen Bergen Norway

Department of Immunology Weizmann Institute of Science Rehovot Israel

Department of Medicine Haukeland University Hospital Bergen Norway

Laboratory of Immunobiology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

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Nat Immunol. 2022 Jul;23(7):997-999. doi: 10.1038/s41590-022-01252-9. PubMed

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The emerging family of RORγt+ antigen-presenting cells

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