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： Si, Wei 1 ; Zhao, Xin 2 ; Li, Ruitong 1 ; Li, Yaopeng 3 ; Ma, Cui 1 ; Zhao, Xiaohan 1 ; Bugno, Jason 4 ; Qin, Yuchang 1 ; Zhang, Junmin 1 ; Liu, Hongwei 5 ; Wang, Liangliang 5 ;
作者机构： 1.Chinese Acad Agr Sci, Inst Anim Sci, State Key Lab Anim Nutr, Beijing, Peoples R China
2.McGill Univ, Dept Anim Sci, Montreal, PQ, Canada
3.Univ Chicago, Pritzker Sch Mol Engn, Chicago, IL USA
4.Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL USA
5.Chinese Acad Sci, Inst Microbiol, Lab Microbiome & Microecol Technol, Beijing, Peoples R China
期刊名称：JOURNAL OF CLINICAL INVESTIGATION （ 影响因子：13.6； 五年影响因子：14.4 ）
ISSN： 0021-9738
年卷期： 2025 年 135 卷 3 期
页码：
收录情况： SCI
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-kappa B (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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