1. A Novel miR-24–TCF1 Axis in Modulating Effector T Cell Responses
- Author
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Cho, Sunglim, Wu, Cheng-Jang, Nguyen, Duc T, Lin, Ling-Li, Chen, Mei-Chi, Khan, Aly Azeem, Yang, Bi-Huei, Fu, Wenxian, and Lu, Li-Fan
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Genetics ,Biotechnology ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Animals ,Cell Differentiation ,Cytokines ,Down-Regulation ,GATA3 Transcription Factor ,Hepatocyte Nuclear Factor 1-alpha ,Interferon-gamma ,Interleukin-17 ,Interleukin-4 ,Lymphocyte Activation ,Mice ,MicroRNAs ,Signal Transduction ,T-Lymphocyte Subsets ,Th1 Cells ,Th17 Cells ,Th2 Cells ,Biochemistry and cell biology - Abstract
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.
- Published
- 2017