Oropharyngeal candidiasis (OPC; thrush) is an opportunistic infection caused by the commensal fungus Candida albicans. Interleukin-17 (IL-17) and IL-22 are cytokines produced by type 17 lymphocytes. Both cytokines mediate antifungal immunity yet activate quite distinct downstream signaling pathways. While much is now understood about how IL-17 promotes immunity in OPC, the activities of IL-22 are far less well delineated. We show that, despite having similar requirements for induction from type 17 cells, IL-22 and IL-17 function nonredundantly during OPC. We find that the IL-22 and IL-17 receptors are required in anatomically distinct locations within the oral mucosa; loss of IL-22RA1 or signal transducer and activator of transcription 3 (STAT3) in the oral basal epithelial layer (BEL) causes susceptibility to OPC, whereas IL-17RA is needed in the suprabasal epithelial layer (SEL). Transcriptional profiling of the tongue linked IL-22/STAT3 not only to oral epithelial cell proliferation and survival but also, unexpectedly, to driving an IL-17–specific gene signature. We show that IL-22 mediates regenerative signals on the BEL that replenish the IL-17RA–expressing SEL, thereby restoring the ability of the oral epithelium to respond to IL-17 and thus to mediate antifungal events. Consequently, IL-22 signaling in BEL “licenses” IL-17 signaling in the oral mucosa, revealing spatially distinct yet cooperative activities of IL-22 and IL-17 in oral candidiasis.

口咽念珠菌病（OPC；鹅口疮）是由共生真菌白色念珠菌引起的机会性感染。白介素 17 (IL-17) 和 IL-22 是 17 型淋巴细胞产生的细胞因子。两种细胞因子介导抗真菌免疫，但激活截然不同的下游信号通路。虽然现在人们对 IL-17 如何促进 OPC 免疫已有很多了解，但对 IL-22 的活性却知之甚少。我们发现，尽管 17 型细胞的诱导要求相似，但 IL-22 和 IL-17 在 OPC 过程中发挥非冗余作用。我们发现口腔粘膜内解剖学上不同的位置需要 IL-22 和 IL-17 受体；口腔基底上皮层 (BEL) 中 IL-22RA1 或信号转导子和转录激活剂 3 (STAT3) 的缺失会导致对 OPC 的易感性，而基底上皮层 (SEL) 中则需要 IL-17RA。舌头的转录谱不仅将 IL-22/STAT3 与口腔上皮细胞增殖和存活联系起来，而且出人意料地还与驱动 IL-17 特异性基因特征相关。我们发现 IL-22 介导 BEL 上的再生信号，补充表达 IL-17RA 的 SEL，从而恢复口腔上皮细胞对 IL-17 的反应能力，从而介导抗真菌事件。因此，BEL 中的 IL-22 信号传导“许可”口腔粘膜中的 IL-17 信号传导，揭示了 IL-22 和 IL-17 在口腔念珠菌病中空间上不同但协同的活性。