Retinoic acid (RA), a vitamin A metabolite, regulates transcriptional programs that drive protective or pathogenic immune responses in the intestine, in a manner dependent on RA concentration. Vitamin A is obtained from diet and is metabolized by intestinal epithelial cells (IECs), which operate in intimate association with microbes and immune cells. Here we found that commensal bacteria belonging to class Clostridia modulate RA concentration in the gut by suppressing the expression of retinol dehydrogenase 7 (Rdh7) in IECs. Rdh7 expression and associated RA amounts were lower in the intestinal tissue of conventional mice, as compared to germ-free mice. Deletion of Rdh7 in IECs diminished RA signaling in immune cells, reduced the IL-22-dependent antimicrobial response, and enhanced resistance to colonization by Salmonella Typhimurium. Our findings define a regulatory circuit wherein bacterial regulation of IEC-intrinsic RA synthesis protects microbial communities in the gut from excessive immune activity, achieving a balance that prevents colonization by enteric pathogens.

中文翻译：

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Commensals抑制肠道上皮细胞视黄酸的合成，以调节白介素22的活性，并防止微生物代谢障碍。

维甲酸（RA），一种维生素A代谢产物，以依赖于RA浓度的方式调节在肠道中驱动保护性或病原性免疫反应的转录程序。维生素A从饮食中获取，并通过肠上皮细胞（IEC）代谢，而上皮细胞则与微生物和免疫细胞密切相关。在这里，我们发现属于梭菌属的共生细菌可通过抑制IECs中视黄醇脱氢酶7（Rdh7）的表达来调节肠道中RA的浓度。与无菌小鼠相比，常规小鼠肠道组织中的Rdh7表达和相关的RA含量较低。在IECs中删除Rdh7可减少免疫细胞中的RA信号传导，减少IL-22依赖性抗菌反应，并增强对鼠伤寒沙门氏菌定植的抵抗力。