Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease.

Alcohol-associated liver disease is accompanied by intestinal mycobiome dysbiosis, yet the impacts on liver disease are unclear. We demonstrate that Candida albicans -specific T helper 17 (Th17) cells are increased in circulation and present in the liver of patients with alcohol-associated liver disease. Chronic ethanol administration in mice causes migration of Candida albicans (C. albicans)-reactive Th17 cells from the intestine to the liver. The antifungal agent nystatin decreased C. albicans- specific Th17 cells in the liver and reduced ethanol-induced liver disease in mice. Transgenic mice expressing T cell receptors (TCRs) reactive to Candida antigens developed more severe ethanol-induced liver disease than transgene-negative littermates. Adoptively transferring Candida -specific TCR transgenic T cells or polyclonal C. albicans -primed T cells exacerbated ethanol-induced liver disease in wild-type mice. Interleukin-17 (IL-17) receptor A signaling in Kupffer cells was required for the effects of polyclonal C. albicans -primed T cells. Our findings indicate that ethanol increases C. albicans -specific Th17 cells, which contribute to alcohol-associated liver disease. [Display omitted] • Alcohol increases intestinal C. albicans -specific Th17 cells that migrate to the liver • An antifungal agent reduces C. albicans -specific Th17 cells in the liver • Adoptive transfer of C. albicans -specific Th17 cells promotes liver disease • C. albicans -specific Th17 cells promote liver disease via IL17ra on Kupffer cells How fungal dysbiosis contributes to alcohol-associated liver disease is unclear. Zeng et al. find that C. albicans -specific Th17 cells increase in the blood and liver of patients with alcohol-associated liver disease. In mice, C. albicans -specific Th17 cells migrate from the intestine to the liver, where they contribute to ethanol-induced liver disease. [ABSTRACT FROM AUTHOR]