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

研究成果: Contribution to journalArticle査読

69 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)235-249
ページ数15
ジャーナルJournal of Experimental Medicine
213
2
DOI
出版ステータス出版済み - 2 8 2016

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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