Background & aims: Liver contains high frequency of group 1 innate lymphoid cells (ILC), which are composed of comparable number of type 1 ILC (ILC1) and natural killer (NK) cells in steady state. Little is known about whether and how the interaction between ILC1 and NK cells affects the development of alcoholic liver disease. Methods: A mouse model of chronic alcohol abuse plus single-binge (Gao-Binge model) was established. The levels of alanine aminotransferase/aspartate aminotransferase, hepatic lipid, and inflammatory cytokines or neutrophils were measured to evaluate the degree of liver injury, steatosis, and inflammation. Flow cytometric analysis, cell depletion, or adoptive transfer were used to interrogate the interaction between ILC1 and NK cells. Results: Upon chronic alcohol consumption, NK cells, but not ILC1, underwent apoptosis, resulting in ILC1 dominance among group 1 ILC. Interleukin (IL) 17A expression was up-regulated, and increased IL17A was mainly derived from liver ILC1 after chronic alcohol feeding. Either depletion of ILC1 or neutralization of IL17A could significantly attenuate liver steatosis, inflammation, and injury in alcohol-fed mice. In contrast, normalization of the ILC1/NK cells ratio through NK cells transfer or expanding NK cells had a significant hepatoprotection against alcohol-induced steatohepatitis. Furthermore, NK cell-derived interferon gamma exerted a protective function via inhibiting IL17A production by liver ILC1 during alcoholic steatohepatitis. Conclusions: This is the first study showing that the interplay between liver ILC1 and NK cells occurs and drives the development of alcoholic steatohepatitis. Our findings support further exploration of liver ILC1 or NK cells as a therapeutic target for the treatment of alcohol-associated liver disease.Keywords: Alcoholic Steatohepatitis; IFN-γ; IL17A; ILC1; NK Cell.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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