Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study
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 (IBD...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2437253 |
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| author | Xiaomin Su Yazheng Yang Yunhuan Gao Juanjuan Wang Yang Hao Yuan Zhang Rongcun Yang |
| author_facet | Xiaomin Su Yazheng Yang Yunhuan Gao Juanjuan Wang Yang Hao Yuan Zhang Rongcun Yang |
| author_sort | Xiaomin Su |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5ce64f64a0884d6e86fe47ed4a3a5dad |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-5ce64f64a0884d6e86fe47ed4a3a5dad2024-12-05T12:53:36ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2437253Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based studyXiaomin Su0Yazheng Yang1Yunhuan Gao2Juanjuan Wang3Yang Hao4Yuan Zhang5Rongcun Yang6Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, ChinaDepartment of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, ChinaDepartment of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, ChinaDepartment of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, ChinaDepartment of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, ChinaDepartment of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, ChinaDepartment of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, ChinaGut 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.https://www.tandfonline.com/doi/10.1080/19490976.2024.2437253Conjugated linoleic acidIL-35macrophagesReg4gut microbiota |
| spellingShingle | Xiaomin Su Yazheng Yang Yunhuan Gao Juanjuan Wang Yang Hao Yuan Zhang Rongcun Yang Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study Gut Microbes Conjugated linoleic acid IL-35 macrophages Reg4 gut microbiota |
| title | Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study |
| title_full | Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study |
| title_fullStr | Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study |
| title_full_unstemmed | Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study |
| title_short | Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study |
| title_sort | gut microbiota cla and il 35 induction in macrophages through gαq 11 mediated stat1 4 pathway an animal based study |
| topic | Conjugated linoleic acid IL-35 macrophages Reg4 gut microbiota |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2437253 |
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