Candida albicans specific Th17 cells with restricted specificities are enriched in the human oral mucosa but transmigrate and adapt in intestinal inflammation 4021

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Abstract Description Th17 cells enhance mucosal barrier function but can drive inflammatory diseases when dysregulated. Candida albicans, a fungal commensal on mucosal tissues, is a potent inducer of human Th17 cells, though the underlying mechanisms remain unclear. This study investigates the specificity and tissue distribution of C. albicans-specific Th17 cells in healthy (HC) and their alterations in intestinal inflammation of Crohn’s disease (CD). Using the antigen-reactive T cell enrichment assay, we compared CD4+ T cell responses to proteins enriched in several sub-cellular fractions of C. albicans, such as biofilm, secreted proteins or extracellular vesicles (EVs). We found that secreted/EV proteins induced strong Th17 responses, in similar frequencies to whole C. albicans-lysate, identifying them as major Th17 cell targets at homeostasis. Surprisingly, C. albicans-specific Th17 cells expressed high levels of the homing marker CLA, but not IntB7 and were at steady state strongly enriched in oral, as compared to intestinal tissue. In patients with CD, increased C. albicans-specific Th17 cells remain focused on the same protein targets but migrate from oral tissue into the inflamed intestine, where they acquire a pathogenic Th17 signature. Our results identify that secreted/EV protein cargo restricts the specificity of anti-C. albicans Th17 cells and provide evidence that initial homeostatic Th17 responses translocating from the oral mucosa to the intestine, may contribute to CD pathology. Topic Categories Mucosal and Regional Immunology (MUC)

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