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ANTIFUNGAL RESPONSES

Extrathymic Aire primes Candida-specific TH17 cells

Nature Immunology volume 23, pages 997–999 (2022)Cite this article

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Extrathymic MHCII+Rorc+ Aire-expressing cells that share characteristics with type 3 innate lymphoid cells (ILC3s) internalize C. albicans and present its antigens, priming the development of Candida-specific TH17 cells.

Thymic expression of the transcriptional regulator Aire is critical for enforcing central immune tolerance1. However, the immunological functions of extrathymic Aire-expressing cells (eTACs) remain incompletely understood. AIRE deficiency causes multi-organ autoimmunity and chronic mucocutaneous candidiasis (CMC), a condition characterized by severe, recurrent mucosal, but not systemic, infections by the commensal fungus Candida albicans, typically affecting the mouth and esophagus1. In this issue of Nature Immunology, Dobeš et al.2 demonstrate that a population of mouse MHCII+Rorc+Aire+ cells that share characteristics with type 3 innate lymphoid cells (ILC3s) can internalize and present C. albicans and prime the generation of Candida-specific TH17 cells, which can contribute to protective IL-17-dependent antifungal defence at mucosal barriers3,4. In this paper, mice with Aire deletion restricted to extrathymic Rorc-expressing cells exhibited reduced numbers of Candida-specific TH17 cells, associated with increased fungal proliferation in kidney and mucosal tissues when challenged in recall models of systemic and mucosal candidiasis.

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Fig. 1: Thymic and extrathymic expression and function of Aire.

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Acknowledgements

This work was supported by the Division of Intramural Research of the NIAID (ZIA AI001175 to M.S.L.).

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  1. Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA

    Vasileios Oikonomou & Michail S. Lionakis

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  1. Vasileios Oikonomou
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  2. Michail S. Lionakis
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Correspondence to Michail S. Lionakis.

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Oikonomou, V., Lionakis, M.S. Extrathymic Aire primes Candida-specific TH17 cells. Nat Immunol 23, 997–999 (2022). https://doi.org/10.1038/s41590-022-01252-9

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