Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease
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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.
Suling Zeng,Elisa Rosati,Carina Saggau,Berith Messner,Huikuan Chu,Yi Duan,Phillipp Hartmann,Yanhan Wang,Shengyun Ma,Wendy Jia Men Huang,Jihyung Lee,Sung Min Lee,Raquel Carvalho-Gontijo,Vivian Zhang,Joseph P Hoffmann,Jay K Kolls,Eyal Raz,David A Brenner,Tatiana Kisseleva,Salomé LeibundGut-Landmann,Petra Bacher,Peter Stärkel,Bernd Schnabl