排序方式: 共有16条查询结果,搜索用时 15 毫秒
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Gustavo J. Martinez Zhengmao Zhang Joseph M. Reynolds Shinya Tanaka Yeonseok Chung Ting Liu Elizabeth Robertson Xia Lin Xin-Hua Feng Chen Dong 《The Journal of biological chemistry》2010,285(38):29039-29043
Development of Foxp3+ regulatory T cells and pro-inflammatory Th17 cells from naive CD4+ T cells requires transforming growth factor-β (TGF-β) signaling. Although Smad4 and Smad3 have been previously shown to regulate Treg cell induction by TGF-β, they are not required in the development of Th17 cells. Thus, how TGF-β regulates Th17 cell differentiation remains unclear. In this study, we found that TGF-β-induced Foxp3 expression was significantly reduced in the absence of Smad2. More importantly, Smad2 deficiency led to reduced Th17 differentiation in vitro and in vivo. In the experimental autoimmune encephalomyelitis model, Smad2 deficiency in T cells significantly ameliorated disease severity and reduced generation of Th17 cells. Furthermore, we found that Smad2 associated with retinoid acid receptor-related orphan receptor-γt (RORγt) and enhanced RORγt-induced Th17 cell generation. These results demonstrate that Smad2 positively regulates the generation of inflammatory Th17 cells. 相似文献
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A critical role of costimulation during intrathymic development of invariant NK T cells 总被引:1,自引:0,他引:1
Chung Y Nurieva R Esashi E Wang YH Zhou D Gapin L Dong C 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(4):2276-2283
CD1d-restricted Valpha14(+) invariant NK T (iNKT) cells are a specialized alphabeta T cell subset that regulates both innate and adaptive immunity. Although costimulatory molecules are required for the activation of conventional T cells and for the development of Foxp3(+) T cells, their role in iNKT cell regulation is unclear. Here we report that mice deficient in CD80/CD86 and/or B7h exhibit severe defects in thymic iNKT cell maturation, associated with largely reduced iNKT cell number in the thymus and the periphery. We show that costimulation is necessary for the optimal expansion of postselected NK1.1(-) immature iNKT cells in the thymus and for the proper expression of the maturation markers T-bet and CD122. Surprisingly, costimulatory molecules on both hemopoietic and nonhematopoietic cells are required for iNKT cell development. Our results thus demonstrate a previously unknown function of costimulation in the intrathymic development of iNKT cells, distinct from that of conventional T cells and regulatory T cells. 相似文献
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Yongliang Zhang Thang Nguyen Peng Tang Norman J. Kennedy Huipeng Jiao Mingliang Zhang Joseph M. Reynolds Anja Jaeschke Natalia Martin-Orozco Yeonseok Chung Wei-min He Chen Wang Weiping Jia Baoxue Ge Roger J. Davis Richard A. Flavell Chen Dong 《The Journal of biological chemistry》2015,290(24):14875-14883
Obesity and metabolic disorders such as insulin resistance and type 2 diabetes have become a major threat to public health globally. The mechanisms that lead to insulin resistance in type 2 diabetes have not been well understood. In this study, we show that mice deficient in MAPK phosphatase 5 (MKP5) develop insulin resistance spontaneously at an early stage of life and glucose intolerance at a later age. Increased macrophage infiltration in white adipose tissue of young MKP5-deficient mice correlates with the development of insulin resistance. Glucose intolerance in MKP5-deficient mice is accompanied by significantly increased visceral adipose weight, reduced AKT activation, enhanced p38 activity, and increased inflammation in visceral adipose tissue when compared with wild-type (WT) mice. Deficiency of MKP5 resulted in increased inflammatory activation in macrophages. These findings thus demonstrate that MKP5 critically controls inflammation in white adipose tissue and the development of metabolic disorders. 相似文献
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MKP-1 Is Necessary for T Cell Activation and Function 总被引:1,自引:0,他引:1
Yongliang Zhang Joseph M. Reynolds Seon Hee Chang Natalia Martin-Orozco Yeonseok Chung Roza I. Nurieva Chen Dong 《The Journal of biological chemistry》2009,284(45):30815-30824
MAPKs are evolutionarily conserved immune regulators. MAPK phosphatases (MKPs) that negatively regulate MAPK activities have recently emerged as critical players in both innate and adaptive immune responses. MKP-1, also known as DUSP1, was previously shown to negatively regulate innate immunity by inhibiting pro-inflammatory cytokine production. Here, we found that MKP-1 is necessary in T cell activation and function. MKP-1 deficiency in T cells impaired the activation, proliferation, and function of T cells in vitro, associated with enhanced activation of JNK and reduced NFATc1 translocation into the nucleus. Consistently, MKP-1−/− mice were defective in anti-influenza immunity in vivo and resistant to experimental autoimmune encephalomyelitis. Our results thus demonstrate that MKP-1 is a critical positive regulator of T cell activation and function and may be targeted in treatment of autoimmune diseases. 相似文献