Cell子刊：肠道真菌失调如何促进酒精肝？
- ①酒精相关肝病患者中，白色念珠菌（Ca）特异性Th17在血液中增多，并存在于肝脏中；
- ②小鼠长期服用酒精可引起Ca特异性Th17从肠道迁移到肝脏；
- ③用抗真菌药减少肠道真菌，可减少小鼠肝脏Ca特异性Th17，减轻酒精诱发的肝病；
- ④表达念珠菌抗原特异性TCR的转基因小鼠有更重的酒精诱发肝病，过继转移这些转基因T细胞或Ca致敏的多克隆T细胞，会加剧野生型小鼠的酒精诱发肝病；
- ⑤Kupffer细胞的IL17ra信号，介导了Ca致敏的多克隆T细胞的促肝病作用。
主编推荐语
酒精相关肝病伴随着肠道真菌群失调，白色念珠菌增多是一大特征，但这种真菌失调对肝病的影响尚不清楚。Cell Host and Microbe发表的一项最新研究，结合患者样本分析和小鼠实验表明，酒精可增加白色念珠菌特异性Th17细胞，这些细胞从肠道迁移至肝脏，通过作用于肝脏Kupffer细胞的IL-17受体A（IL17ra）信号，发挥促进酒精诱导的肝病的作用。用抗真菌药物抑制酒精引起的白色念珠菌过度增殖，或能通过降低白色念珠菌特异性Th17应答，改善酒精相关肝病。
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Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease
白色念珠菌特异性Th17细胞介导的应答促进酒精相关性肝病
10.1016/j.chom.2023.02.001
03-08, Article
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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.
First Authors:
Suling Zeng
Correspondence Authors:
Bernd Schnabl
All Authors:
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
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