IL-17RA signaling in oral epithelium is necessary and sufficient for protection against oropharyngeal candidiasis

Impairments in IL-17 signaling components (IL-17RA, IL-17RC, Act1) cause oropharyngeal candidiasis (OPC) in mice and humans. Antifungal signaling by IL-17 occurs in mesenchymal and epithelial cells but also hematopoietic cells. Expression profiling revealed remarkable similarities between C. albicans-infected human oral epithelial cells (OECs) and infected murine tongue, suggesting that OECs are an essential IL-17-responsive cell type. We created a conditional knockout mouse expressing CRE driven by the Keratin (K)-13 promoter (K13CRE), which exhibited specificity for suprabasal oral and esophageal epithelium. K13CRE x Il17rafl/fl mice (Il17ra?K13) had fungal loads and symptoms comparable to Il17ra-/-. RNA-Seq analyses suggested that OEC-dependent IL-17 signaling impairs antimicrobial peptides, particularly Defb3 (Alpha defensin 3). Thus, OECs, not hematopoietic cells, dominantly control the IL-17-dependent response to OPC, with particularly potent effects on AMP expression.