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

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

PROVIDER: PRJNA891300 | ENA |

REPOSITORIES: ENA

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Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease [scRNA & scTCR-seq]

Project description:Alcohol-associated liver disease is accompanied by changes in the intestinal mycobiome. How fungal dysbiosis contributes to liver disease is not clear. T-helper (Th17) cells mediate immune responses against fungi, but the interleukin 17 (IL17) pathway has been associated with pathogenesis of alcohol-associated liver disease. Here, we demonstrate that Candida albicans (C. albicans)-specific Th17 cells are increased in the circulation and present in the liver of patients with alcohol-associated liver disease. Chronic ethanol administration to mice results in migration of C. albicans-reactive Th17 cells from the intestine to the liver. The antifungal agent nystatin reduced intestinal fungal overgrowth, decreased C. albicans-specific Th17 cells in the liver, and reduced features of ethanol-induced liver disease in mice. Transgenic mice that express a T-cell receptor (TCR) reactive to Candida antigens develop more severe ethanol-induced liver disease than transgene-negative littermates; disease severity was reduced by administration of an antibody against IL17 to the TCR transgenic mice. Adoptive transfer of C. albicans-reactive Th17 cells exacerbated ethanol-induced liver disease in wild-type mice. IL17 receptor A (IL17ra) signaling in Kupffer cells was required for the effects of C. albicans-reactive Th17 cells. Our findings indicate that ethanol increases C. albicans-reactive Th17 cells, which contribute to alcohol-associated liver disease.

2023-02-16 | GSE215930 | GEO

Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease [bulk TCR-seq]

2023-02-16 | GSE215929 | GEO

Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease [bulk TCR-seq]

Project description:Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease [bulk TCR-seq]

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Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease [scRNA & scTCR-seq]

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Extrathymic expression of Aire controls the induction of effective TH17 cell-mediated immune response to Candida albicans

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