JEM:浙江大学鲁林荣教授课题组发表T细胞分化和自身免疫性炎症
2017年4月11日，国际免疫学领域重要的顶级期刊、洛克菲勒大学出版社的旗舰杂志《Journal of Experimental Medicine》在线发表了浙江大学医学院免疫学研究所鲁林荣教授课题组的最新研究成果 “Suppression of Th17 cell differentiation by Misshapen/NIK-related kinase MINK1”，该研究揭示了T细胞分化和自身免疫性炎症应答调控的新机制。研究第一作者为浙江大学免疫学研究所博士生付国通，免疫学研究所王建莉研究员和鲁林荣教授为论文通讯作者。
以分泌IL-17A, IL-17F, IL-22等细胞因子为主的Th17细胞，是新近发现不同于Th1和Th2细胞的一种致炎性Th细胞(辅助性T细胞)。Th17细胞在维持肠道稳态和抵抗胞外细菌、真菌感染的宿主防御中起到重要作用。而Th17的异常也是导致自身免疫疾病发生的关键性因素之一。本研究利用基因敲除小鼠模型发现GCK家族激酶MINK1能抑制Th17细胞的分化。 MINK1通过直接磷酸化SMAD2蛋白α1螺旋区域的T324位点阻断TGF-β诱导的SMAD2活化，进而抑制Th17细胞的产生。通过进一步构建小鼠实验性自身免疫性脑脊髓炎(EAE)模型，本研究明确了MINK1在Th17细胞介导的自身免疫性炎症中的重要作用。更深入的研究揭示，ROS(活性氧自由基)抑制剂N-乙酰半胱氨酸(NAC)能以依赖于MNIK1的方式促进Th17细胞分化，且喂食NAC能增加T细胞诱发小鼠自身免疫性脑脊髓炎的致病性。该研究提示了抗氧化剂的补充摄入可能有促进自身免疫性疾病发生和发展的风险。
ROS suppresses Th17 Cell differentiation through the activation of MINK1 kinase.
原文链接：
Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
原文摘要：
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.
作者：鲁林荣
