日本庆应义塾大学研究人员最新发现，如果人为使一种蛋白质在未成熟的T细胞内大量表达，T细胞就难以分化成辅助性T细胞17(Th17细胞)。这项成果有助于治疗Th17过度作用导致的类风湿性关节炎、多发性硬化症等自体免疫疾病。
根据庆应义塾大学发布的新闻公报，该校医学系教授吉村昭彦领导的小组经实验发现，未成熟的T细胞要成熟并分化成Th17细胞，蛋白质“Eomesodermin”的量必须减少，如果人为令这种蛋白质在未成熟的T细胞内大量表达，Th17细胞就会显著减少。
研究人员还发现，要使“Eomesodermin”的量减少，必须要有一种名为JNK的磷酸化酶。他们在实验中给多发性硬化症模型鼠使用JNK阻断剂，结果实验鼠的症状有了明显改善。
公报说，如果能提高T细胞中“Eomesodermin”的表达，或者抑制JNK的活性，就有望研发出治疗自体免疫疾病的新方法。
辅助性T细胞在免疫系统中承担着举足轻重的作用，它们会根据入侵病原体种类的不同，分化成Th1、Th2和Th17三种类型中的一种，进而诱导针对入侵病原体最适合的免疫应答。而另一方面，如果辅助性T细胞过度作用就可能引发自体免疫疾病。比如，Th2过量生成就会引起花粉或者食物过敏；而Th17过度作用会引发类风湿性关节炎、多发性硬化症和牛皮癣等自体免疫疾病。相关研究论文发表在美国《免疫》杂志网络版上。（生物谷Bioon.com）
生物谷推荐原文出处：
Immunity doi:10.1016/j.immuni.2011.02.021
Transcription Factor Smad-Independent T Helper 17 Cell Induction by Transforming-Growth Factor-β Is Mediated by Suppression of Eomesodermin
Kenji Ichiyama, Takashi Sekiya, Naoko Inoue, Taiga Tamiya, Ikko Kashiwagi, Akihiro Kimura, Rimpei Morita, Go Muto, Takashi Shichita, Reiko Takahashi and Akihiko Yoshimura
Summary
Transforming growth factor-β (TGF-β) has been shown to be required for Th17 cell differentiation via Smad-independent mechanisms. The molecular mechanism underlying this pathway remains to be clarified, however. We searched for genes regulated by TGF-β through the Smad-independent pathway by using Smad2 and Smad3 double-deficient T cells and identified the transcription factor Eomesodermin (Eomes), whose expression was suppressed by TGF-β via the c-Jun N-terminal kinase (JNK)-c-Jun signaling pathway. Inhibition of JNK strongly suppressed disease in an in vivo EAE model as well as in vitro Th17 cell induction. Overexpression of Eomes substantially suppressed Th17 cell differentiation, whereas ablation of Eomes expression could substitute for TGF-β in Th17 cell induction in primary T cells. Eomes suppressed Rorc and Il17a promoters by directly binding to the proximal region of these promoters. In conclusion, the suppression of Eomes by TGF-β via the JNK pathway is an important mechanism for Smad-independent Th17 cell differentiation.
Graphical Abstract
Highlights
Suppression of Eomes by TGF-β is an important mechanism for Th17 cell differentiation ? Eomes expression is suppressed by TGF-β via a Smad-independent mechanism ? The JNK-c-Jun pathway suppresses Eomes expression and promotes Th17 cell differentiation ? Eomes directly inhibits RORγt and IL-17A expression through the T-box domain..
