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Lactobacillus rhamnosus GG induces STING-dependent IL-10 in intestinal monocytes and alleviates inflammatory colitis in mice

文献类型： 外文期刊

作者： Wei Si;Xin Zhao;Ruitong Li;Yaopeng Li;Cui Ma;Xiaohan Zhao;Jason Bugno;Yuchang Qin;Junmin Zhang;Hongwei Liu;Liangliang Wang

作者机构：

期刊名称： Journal of Clinical Investigation

ISSN： 0021-9738

年卷期： 2025 年 135 卷 3 期

页码：

收录情况： SCIE（2025版）

摘要： Preclinical and clinical observations indicate that the probiotic Lactobacillus rhamnosus GG (LGG) can modulate colonic inflammation. However, the underlying mechanisms have not been explored in depth. Here, we demonstrate that oral administration of live LGG alleviated inflammatory colitis by increasing IL-10 expression in intestinal Ly6C+ monocytes. Mechanistically, LGG induced IL-10 production via the stimulator of IFN genes (STING)/TBK1/NF-κB (RELA) signaling pathway in intestinal Ly6C+ monocytes, enhancing their immune-suppressive function. Elevated IL-10 subsequently activated IL-10 signaling in Ly6C+ monocytes, resulting in an IL-10–based autocrine regulatory loop and inhibition of proinflammatory cytokine production. Furthermore, LGG shifted the gut microbial community and its metabolic functions, leading to intestinal immune responses against colitis. Fecal microbiota transplantation from LGG-colonized mice alleviated immune checkpoint blockade–associated colitis. Our findings highlight the importance of STING signaling in IL-10–dependent antiinflammatory immunity and establish an empirical basis for developing oral administration of live LGG as an efficient and safe therapeutic strategy against inflammatory colitis.

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