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miR-23~27~24 clusters control effector T cell differentiation and function

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Item Type:Article
Title:miR-23~27~24 clusters control effector T cell differentiation and function
Creators Name:Cho, S. and Wu, C.J. and Yasuda, T. and Cruz, L.O. and Khan, A.A. and Lin, L.L. and Nguyen, D.T. and Miller, M. and Lee, H.M. and Kuo, M.L. and Broide, D.H. and Rajewsky, K. and Rudensky, A.Y. and Lu, L.F.
Abstract:Coordinated repression of gene expression by evolutionarily conserved microRNA (miRNA) clusters and paralogs ensures that miRNAs efficiently exert their biological impact. Combining both loss- and gain-of-function genetic approaches, we show that the miR-23~27~24 clusters regulate multiple aspects of T cell biology, particularly helper T (Th) 2 immunity. Low expression of this miRNA family confers proper effector T cell function at both physiological and pathological settings. Further studies in T cells with exaggerated regulation by individual members of the miR-23~27~24 clusters revealed that miR-24 and miR-27 collaboratively limit Th2 responses through targeting IL-4 and GATA3 in both direct and indirect manners. Intriguingly, although overexpression of the entire miR-23 cluster also negatively impacts other Th lineages, enforced expression of miR-24, in contrast to miR-23 and miR-27, actually promotes the differentiation of Th1, Th17, and induced regulatory T cells, implying that under certain conditions, miRNA families can fine tune the biological effects of their regulation by having individual members antagonize rather than cooperate with each other. Together, our results identify a miRNA family with important immunological roles and suggest that tight regulation of miR-23~27~24 clusters in T cells is required to maintain optimal effector function and to prevent aberrant immune responses.
Keywords:Animal Disease Models, Asthma, Cell Differentiation, GATA3 Transcription Factor, Gene Expression Regulation, Gene Regulatory Networks, Helper-Inducer T-Lymphocytes, Interleukin-4, Lymphocyte Activation, MicroRNAs, Multigene Family, Phenotype, T-Lymphocyte Subsets, Th2 Cells, Transgenic Mice, Animals, Mice
Source:Journal of Experimental Medicine
Publisher:Rockefeller University Press
Page Range:235-249
Date:8 February 2016
Official Publication:https://doi.org/10.1084/jem.20150990
PubMed:View item in PubMed

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