Cell子刊:肠道真菌失调如何促进酒精肝?
创作:Sunflower 审核:mildbreeze 04月01日
  • 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;
  • 小鼠长期服用酒精可引起Ca特异性Th17从肠道迁移到肝脏;
  • 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;
  • 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;
  • Kupffer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。
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mildbreeze
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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