Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study
| Autor: | Xiaomin Su, Yazheng Yang, Yunhuan Gao, Juanjuan Wang, Yang Hao, Yuan Zhang, Rongcun Yang |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Gut Microbes, Vol 16, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 19490976 1949-0984 1949-0976 |
| DOI: | 10.1080/19490976.2024.2437253 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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