Cho Sunglim, Wu Cheng-Jang, Nguyen Duc T, Lin Ling-Li, Chen Mei-Chi, Khan Aly Azeem, Yang Bi-Huei, Fu Wenxian, Lu Li-Fan
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
Toyota Technological Institute at Chicago, Chicago, IL 60637.
J Immunol. 2017 May 15;198(10):3919-3926. doi: 10.4049/jimmunol.1601404. Epub 2017 Apr 12.
miR-23∼27∼24 was recently implicated in restricting Th2 immunity, as well as the differentiation and function of other effector T cell lineages. Interestingly, miR-24, unlike other family members, actually promotes Th1 and Th17 responses. In this article, we show that miR-24 drives the production of IFN-γ and IL-17 in T cells at least in part through targeting TCF1, a transcription factor known for its role in limiting Th1 and Th17 immunity. Surprisingly, whereas TCF1 was previously shown to promote Th2 responses through inducing GATA3, enforced TCF1 expression in miR-24-overexpressing T cells led to further downregulation of IL-4 and GATA3 expression, suggesting miR-24-mediated inhibition of Th2 immunity cannot be attributed to TCF1 repression by miR-24. Together, our data demonstrate a novel miR-24-TCF1 pathway in controlling effector cytokine production by T cells and further suggest miR-24 could function as a key upstream molecule regulating TCF1-mediated immune responses.
最近研究表明,miR-23∼27∼24参与限制Th2免疫反应以及其他效应T细胞谱系的分化和功能。有趣的是,与其他家族成员不同,miR-24实际上促进Th1和Th17反应。在本文中,我们发现miR-24至少部分通过靶向TCF1来驱动T细胞中IFN-γ和IL-17的产生,TCF1是一种已知在限制Th1和Th17免疫中起作用的转录因子。令人惊讶的是,虽然之前研究表明TCF1通过诱导GATA3来促进Th2反应,但在过表达miR-24的T细胞中强制表达TCF1会导致IL-4和GATA3表达进一步下调,这表明miR-24介导的对Th2免疫的抑制不能归因于miR-24对TCF1的抑制。总之,我们的数据揭示了一条新的miR-24-TCF1途径,该途径控制T细胞效应细胞因子的产生,并进一步表明miR-24可能作为调节TCF1介导的免疫反应的关键上游分子发挥作用。