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

Sunglim Cho, Cheng Jang Wu, Tomoharu Yasuda, Leilani O. Cruz, Aly Azeem Khan, Ling Li Lin, Duc T. Nguyen, Marina Miller, Hyang Mi Lee, Ming Ling Kuo, David H. Broide, Klaus Rajewsky, Alexander Y. Rudensky, Li Fan Lu

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)235-249
Number of pages15
JournalJournal of Experimental Medicine
Volume213
Issue number2
DOIs
Publication statusPublished - Feb 8 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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