当前位置: X-MOL 学术Gut Microbes › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study.
Gut Microbes ( IF 12.2 ) Pub Date : 2024-12-05 , DOI: 10.1080/19490976.2024.2437253
Xiaomin Su,Yazheng Yang,Yunhuan Gao,Juanjuan Wang,Yang Hao,Yuan Zhang,Rongcun Yang

Gut microbiota/metabolites not only participate in the food and energy metabolism but also contribute to the host immune response and homeostasis. The alternation of gut microbiota/metabolites has been widely related to intestinal and extra-intestinal disorders such as intestinal bowel diseases (IBDs). Bactericidal substances from gut epithelial cells can regulate the composition of gut microbiota. However, the effects of regenerating protein 4 (REG4) (human)/(Reg4) (mice), a potentially bactericidal substance from gut epithelial cells, on the gut immune homeostasis maintain elusive. Here, we found that REG4/Reg4 is essential in maintaining gut immune homeostasis through REG4/Reg4 associated gut microbiota. Reg4 knockout (KO) mice were highly sensitive to DSS-mediated colitis, whereas human REG4 intestine epithelial cell transgenic (huREG4IECtg) mice exhibited more resistance to DSS-mediated colitis. Mechanistically, sequencing of gut microbiota and liquid chromatography-mass spectrometry showed that REG4/Reg4 could affect the composition of gut microbiota. REG4/Reg4 associated gut microbiota such as Lactobacillus could metabolize linoleic acid (LA) into conjugated linoleic acid (CLA). Immunoprecipitation and immunoblot showed that CLA could effectively promote the expression of IL-35 in macrophages through Gαq/11 mediated activation STAT1/4. Thus, our results demonstrate that REG4/Reg4 plays a critical role in maintaining gut immune homeostasis through CLA-mediated IL-35+ macrophages.

中文翻译:


通过 Gαq/11 介导的 STAT1/4 途径在巨噬细胞中诱导肠道微生物群 CLA 和 IL-35:一项基于动物的研究。



肠道微生物群/代谢物不仅参与食物和能量代谢,还有助于宿主的免疫反应和体内平衡。肠道微生物群/代谢物的交替与肠道和肠道外疾病(如肠道疾病 (IBD))广泛相关。来自肠道上皮细胞的杀菌物质可以调节肠道微生物群的组成。然而,再生蛋白 4 (REG4) (人)/(Reg4) (小鼠)(一种来自肠道上皮细胞的潜在杀菌物质)对肠道免疫稳态的影响仍然难以捉摸。在这里,我们发现 REG4/Reg4 通过 REG4/Reg4 相关肠道微生物群维持肠道免疫稳态是必不可少的。Reg4 敲除 (KO) 小鼠对 DSS 介导的结肠炎高度敏感,而人 REG4 肠上皮细胞转基因 (huREG4IECtg) 小鼠对 DSS 介导的结肠炎表现出更强的耐药性。从机制上讲,肠道菌群测序和液相色谱-质谱法表明 REG4/Reg4 可影响肠道菌群的组成。REG4/Reg4 相关的肠道微生物群(如乳酸杆菌)可以将亚油酸 (LA) 代谢为共轭亚油酸 (CLA)。免疫沉淀和免疫印迹显示,CLA 可通过 Gαq/11 介导的激活 STAT1/4 有效促进巨噬细胞中 IL-35 的表达。因此,我们的结果表明,REG4/Reg4 通过 CLA 介导的 IL-35 + 巨噬细胞在维持肠道免疫稳态中起关键作用。
更新日期:2024-12-05
down
wechat
bug