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 journalArticle

49 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 - Jan 1 2016

Fingerprint

MicroRNAs
Cell Differentiation
T-Lymphocytes
Regulatory T-Lymphocytes
Interleukin-4
Cell Biology
Immunity
Gene Expression

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Cho, S., Wu, C. J., Yasuda, T., Cruz, L. O., Khan, A. A., Lin, L. L., ... Lu, L. F. (2016). miR-23~27~24 clusters control effector T cell differentiation and function. Journal of Experimental Medicine, 213(2), 235-249. https://doi.org/10.1084/jem.20150990

miR-23~27~24 clusters control effector T cell differentiation and function. / Cho, Sunglim; Wu, Cheng Jang; Yasuda, Tomoharu; Cruz, Leilani O.; Khan, Aly Azeem; Lin, Ling Li; Nguyen, Duc T.; Miller, Marina; Lee, Hyang Mi; Kuo, Ming Ling; Broide, David H.; Rajewsky, Klaus; Rudensky, Alexander Y.; Lu, Li Fan.

In: Journal of Experimental Medicine, Vol. 213, No. 2, 01.01.2016, p. 235-249.

Research output: Contribution to journalArticle

Cho, S, Wu, CJ, Yasuda, T, Cruz, LO, Khan, AA, Lin, LL, Nguyen, DT, Miller, M, Lee, HM, Kuo, ML, Broide, DH, Rajewsky, K, Rudensky, AY & Lu, LF 2016, 'miR-23~27~24 clusters control effector T cell differentiation and function', Journal of Experimental Medicine, vol. 213, no. 2, pp. 235-249. https://doi.org/10.1084/jem.20150990
Cho, Sunglim ; Wu, Cheng Jang ; Yasuda, Tomoharu ; Cruz, Leilani O. ; Khan, Aly Azeem ; Lin, Ling Li ; Nguyen, Duc T. ; Miller, Marina ; Lee, Hyang Mi ; Kuo, Ming Ling ; Broide, David H. ; Rajewsky, Klaus ; Rudensky, Alexander Y. ; Lu, Li Fan. / miR-23~27~24 clusters control effector T cell differentiation and function. In: Journal of Experimental Medicine. 2016 ; Vol. 213, No. 2. pp. 235-249.
@article{c5e199c942914e0cb5ac73c4970c3a8e,
title = "miR-23~27~24 clusters control effector T cell differentiation and function",
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.",
author = "Sunglim Cho and Wu, {Cheng Jang} and Tomoharu Yasuda and Cruz, {Leilani O.} and Khan, {Aly Azeem} and Lin, {Ling Li} and Nguyen, {Duc T.} and Marina Miller and Lee, {Hyang Mi} and Kuo, {Ming Ling} and Broide, {David H.} and Klaus Rajewsky and Rudensky, {Alexander Y.} and Lu, {Li Fan}",
year = "2016",
month = "1",
day = "1",
doi = "10.1084/jem.20150990",
language = "English",
volume = "213",
pages = "235--249",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "2",

}

TY - JOUR

T1 - miR-23~27~24 clusters control effector T cell differentiation and function

AU - Cho, Sunglim

AU - Wu, Cheng Jang

AU - Yasuda, Tomoharu

AU - Cruz, Leilani O.

AU - Khan, Aly Azeem

AU - Lin, Ling Li

AU - Nguyen, Duc T.

AU - Miller, Marina

AU - Lee, Hyang Mi

AU - Kuo, Ming Ling

AU - Broide, David H.

AU - Rajewsky, Klaus

AU - Rudensky, Alexander Y.

AU - Lu, Li Fan

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84960335745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960335745&partnerID=8YFLogxK

U2 - 10.1084/jem.20150990

DO - 10.1084/jem.20150990

M3 - Article

C2 - 26834155

AN - SCOPUS:84960335745

VL - 213

SP - 235

EP - 249

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 2

ER -