据报道，白介素 22 (IL-22) 在多种肝损伤模型中具有保肝作用，包括酒精相关性肝病 (ALD)。然而，IL-22 在酒精性肝炎中的肠道作用仍有待阐明。在喂食酒精 8 周的小鼠中测量肠道 IL-22 水平。然后将 IL-22 给予酒精喂养的小鼠，以测试其对缓解酒精性肝炎的保护作用，重点是肠道保护。对小鼠进行急性 IL-22 治疗，以进一步探讨 IL-22 与抗菌肽 (AMP) 诱导之间的联系。生成肠上皮细胞特异性敲除信号转导子和转录激活子 3 (STAT3) 小鼠，并用于类器官研究，探讨其在 IL-22 介导的 AMP 表达和肠道屏障完整性中的作用。 酒精喂养 8 周后，小鼠肠道内 IL-22 水平显着降低。 IL-22 治疗酒精喂养的小鼠可减轻肝损伤，血清转氨酶水平正常化，改善肝脏组织学，减少脂质积累，并减轻炎症。在肠道中，IL-22 治疗可逆转酒精降低的 Reg3γ 和 α-防御素水平。 IL-22 还可以改善酒精喂养小鼠的肠道屏障完整性并减少内毒素血症。虽然酒精喂养显着减少了阿克曼氏菌，但给予 IL-22 却显着增加了小鼠体内的这种共生细菌。无论是否饮酒，急性 IL-22 治疗都能快速而强烈地诱导肠道 AMP 和 STAT3 激活。通过使用从WT小鼠和肠上皮-STAT3缺陷小鼠中分离的体外培养的肠类器官，我们进一步证明STAT3是IL-22介导的AMP表达所必需的。此外，IL-22 还通过 STAT3 直接调节钠氢交换器 3 来调节肠上皮分化。我们的研究表明，IL-22 不仅针对肝脏，而且在许多方面对肠道有益。 IL-22 的肠道作用包括调节 AMP 表达、微生物群和肠道屏障功能，这对于改善酒精诱导的肠道源性细菌病原体易位和肝脏炎症至关重要。版权所有 © 2023 Yue、Wei、Hao、Dong、Guo、Sun 、赵、周、钟。

The hepatoprotective effect of interleukin 22 (IL-22) has been reported in several models of liver injuries, including alcohol-associated liver disease (ALD). However, the intestinal role of IL-22 in alcoholic hepatitis remains to be elucidated.Intestinal IL-22 levels were measured in mice fed with alcohol for 8 weeks. IL-22 was then administered to alcohol-fed mice to test its protective effects on alleviating alcoholic hepatitis, focusing on intestinal protection. Acute IL-22 treatment was conducted in mice to further explore the link between IL-22 and the induction of antimicrobial peptide (AMP). Intestinal epithelial cell-specific knockout of signal transducer and activator of transcription 3 (STAT3) mice were generated and used for organoid study to explore its role in IL-22-mediated AMP expression and gut barrier integrity.After alcohol feeding for 8 weeks, the intestinal levels of IL-22 were significantly reduced in mice. IL-22 treatment to alcohol-fed mice mitigated liver injury as indicated by normalized serum transaminase levels, improved liver histology, reduced lipid accumulation, and attenuated inflammation. In the intestine, alcohol-reduced Reg3γ and α-defensins levels were reversed by IL-22 treatment. IL-22 also improved gut barrier integrity and decreased endotoxemia in alcohol-fed mice. While alcohol feeding significantly reduced Akkermansia, IL-22 administration dramatically expanded this commensal bacterium in mice. Regardless of alcohol, acute IL-22 treatment induced a fast and robust induction of intestinal AMPs and STAT3 activation. By using in vitro cultured intestinal organoids isolated from WT mice and mice deficient in intestinal epithelial-STAT3, we further demonstrated that STAT3 is required for IL-22-mediated AMP expression. In addition, IL-22 also regulates intestinal epithelium differentiation as indicated by direct regulation of sodium-hydrogen exchanger 3 via STAT3.Our study suggests that IL-22 not only targets the liver but also benefits the intestine in many aspects. The intestinal effects of IL-22 include regulating AMP expression, microbiota, and gut barrier function that is pivotal in ameliorating alcohol induced translocation of gut-derived bacterial pathogens and liver inflammation.Copyright © 2023 Yue, Wei, Hao, Dong, Guo, Sun, Zhao, Zhou and Zhong.