Extrathymic expression of Aire controls the induction of effective TH17 cell-mediated immune response to Candida albicans
Extrathymic expression of Aire controls the induction of effective TH17 cell-mediated immune response to Candida albicans
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DOI：
10.1038/s41590-022-01247-6
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发表时间：
2022-06-27
影响因子：
30.5
通讯作者：
Abramson, Jakub
中科院分区：
文献类型：
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作者：
Dobes, Jan;Ben-Nun, Osher;Abramson, Jakub
编码中枢耐受性 AIRE 主调节因子的基因功能丧失的患者患有一种称为 1 型自身免疫性多内分泌综合征 (APS-1) 的破坏性疾病，其特征是一系列自身免疫性疾病和严重的皮肤粘膜念珠菌病。尽管 APS-1 患者发生自身免疫的关键机制已经明确，但白色念珠菌感染易感性增加的根本原因仍不清楚。在这里，我们证明 Aire(+)MHCII(+) 3 型先天淋巴细胞 (ILC3) 可以感知、内化和呈递白色念珠菌，并在诱导念珠菌特异性 T 辅助细胞 17 (T(H)17) 细胞克隆中发挥关键作用。胸腺外 Rorc-Cre 介导的 Aire 缺失导致念珠菌特异性 T(H)17 细胞生成受损，随后粘膜组织中白色念珠菌过度生长。总的来说，我们的观察发现了一种以前未被认识的针对真菌感染的有效防御反应的调节机制。Abramson 及其同事表明，Aire(+)MHCII(+) ILC3 能够感知、内化和呈现白色念珠菌，并调节白色念珠菌特异性 T(H)17 细胞的诱导。
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.Abramson and colleagues show that Aire(+)MHCII(+) ILC3s sense, internalize and present Candida albicans and modulate the induction of C. albicans-specific T(H)17 cells.