Ascl2 facilitates IL-10 production in Th17 cells to restrain their pathogenicity in inflammatory bowel disease
| Autor: | Zhou Zhou, Xue Yang, Yaxin Song, Caiping Gao, Shan Lei, Jinxia Wang, Liangping Li, Zhenzhen Guo, Qian Yi |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes T cell Biophysics Biology Biochemistry Inflammatory bowel disease Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine medicine Basic Helix-Loop-Helix Transcription Factors Animals Humans Colitis Molecular Biology Gene Autoimmune disease Mechanism (biology) Cell Differentiation Cell Biology medicine.disease Inflammatory Bowel Diseases Gastrointestinal Microbiome Interleukin-10 Interleukin 10 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Th17 Cells Positive Regulatory Domain I-Binding Factor 1 |
| Zdroj: | Biochemical and biophysical research communications. 510(3) |
| ISSN: | 1090-2104 |
| Popis: | Inflammatory bowel disease (IBD) has been well-documented as a chronic gastrointestinal autoimmune disease, but its etiology remains to be elusive. Ascl2 (achaete-scute complex homologue 2), identified as a homologue of the Drosophila achaete-scute gene, has been shown to play an essential for the pathogenesis of autoimmune diseases and cancers. However, whether it is associated with the pathogenesis of IBD remains unclear. Here, we demonstrated that Ascl2 was greatly down-regulated in human IBD and experimental colitis. Interestingly, CD4+ T cell expression of Ascl2 was regulated by intestinal microbiota. Moreover, we revealed that Ascl2 inhibited the differentiation of Th17 cells and restrained their pathogenicity through facilitating IL-10 production. We further showed that Blimp-1 might be involved in the Ascl2-inducing IL-10 expression in CD4+ T cells under Th17 differentiating condition. Notably, lentivirus-mediated overexpression of Ascl2 remarkably alleviated the severity of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis in mice, with decreased level of colonic IL-17A. Our findings demonstrated an unappreciated mechanism whereby Ascl2 negatively modulates pathogenic Th17 cell differentiation via promoting IL-10 production, and alleviates intestinal inflammation. Thus, Ascl2 may serve as a novel therapeutic target of IBD. |
| Databáze: | OpenAIRE |
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