Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
| العنوان: | Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1 |
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| المؤلفون: | Di Wang, Shunli Dong, Xuetao Cao, Linrong Lu, Xuexiao Jin, Yuanjun Qiu, Guotong Fu, Yuehai Ke, Hu Hu, Qin Xu, Harvey Cantor, Xiang Gao, Ting Xu, Jianli Wang |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | The Rockefeller University Press, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, animal structures, Cellular differentiation, Immunology, Regulator, Biology, Article, 03 medical and health sciences, MINK1, Transforming Growth Factor beta, medicine, Immunology and Allergy, Research Articles, chemistry.chemical_classification, Reactive oxygen species, Kinase, Experimental autoimmune encephalomyelitis, Germinal center, Cell Differentiation, medicine.disease, Molecular biology, Cell biology, 030104 developmental biology, chemistry, Phosphorylation, Th17 Cells, Reactive Oxygen Species |
| الوصف: | Fu et al. demonstrate that reactive oxygen species (ROS)–sensing molecule misshapen/NIK-related kinase 1 (MINK1) can specifically suppress Th 17 cell differentiation through direct phosphorylation of SMAD2. This study provides the mechanism of how ROS limit inflammatory response and unveils the potential health risk of antioxidant supplementation. T helper type 17 cells (Th17 cells) are major contributors to many autoimmune diseases. In this study, we demonstrate that the germinal center kinase family member MINK1 (misshapen/NIK-related kinase 1) negatively regulates Th17 cell differentiation. The suppressive effect of MINK1 on induction of Th17 cells is mediated by the inhibition of SMAD2 activation through direct phosphorylation of SMAD2 at the T324 residue. The importance of MINK1 to Th17 cell differentiation was strengthened in the animal model of experimental autoimmune encephalomyelitis (EAE). Moreover, we show that the reactive oxygen species (ROS) scavenger N-acetyl cysteine boosts Th17 cell differentiation in a MINK1-dependent manner and exacerbates the severity of EAE. Thus, we have not only established MINK1 as a critical regulator of Th17 cell differentiation, but also clarified that accumulation of ROS may limit the generation of Th17 cells. The contribution of MINK1 to ROS-regulated Th17 cell differentiation may suggest an important mechanism for the development of autoimmune diseases influenced by antioxidant dietary supplements. |
| اللغة: | English |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3003b6cf6f579ed0850c82669a31ced9 http://europepmc.org/articles/PMC5413330 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3003b6cf6f579ed0850c82669a31ced9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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