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MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis

Nature Immunology volume 10, pages 1252–1259 (2009)Cite this article

A Corrigendum to this article was published on 01 June 2010

This article has been updated

Abstract

Interleukin 17 (IL-17)-producing T helper cells (TH-17 cells) are increasingly recognized as key participants in various autoimmune diseases, including multiple sclerosis. Although sets of transcription factors and cytokines are known to regulate TH-17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a TH-17 cell–associated microRNA, miR-326, whose expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). In vivo silencing of miR-326 resulted in fewer TH-17 cells and mild EAE, and its overexpression led to more TH-17 cells and severe EAE. We also found that miR-326 promoted TH-17 differentiation by targeting Ets-1, a negative regulator of TH-17 differentiation. Our data show a critical role for microRNA in TH-17 differentiation and the pathogenesis of multiple sclerosis.

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Figure 1: Upregulation of miR-326 in patients with multiple sclerosis.
Figure 2: Regulation of EAE development by miR-326.
Figure 3: In vivo generation of TH-17 cells in EAE mice is enhanced by miR-326.
Figure 4: Promotion of in vitro TH-17 differentiation by miR-326.
Figure 5: Ets-1 is a functional target of miR-326.

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Change history

  • 04 December 2009

    In the version of this article initially published, the Actin loading control blot for the top blot is missing from Figure 5c. The error has been corrected in the HTML and PDF versions of the article. In the version of the ONLINE METHODS originally posted online, the description of the lentiviral vector was incorrect. The text in the left column, line 28, should read "...was cloned, downstream of the cytomegalovirus promoter, into a modified lentiviral vector generated from pCDH-CMVMCS-EF1-copGFP (CD511B-1; System Bioscience), in which EF1-copGFP was replaced with IRES-eGFP." The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank C. Dong (Anderson Cancer Center, Houston) for retrovector RV-GFP; X. Liu (Shanghai Institute for Biological Sciences) for fluorescein isothiocyanate–conjugated antibody to mouse T cell antigen receptor γδ; C. Wu (Sun Yat-sen University) for phycoerythrin-conjugated antibody to human CCR6; J. Zhao, L. Wei, Y. Shi, Q. Jing and G. Gao for discussions; and J. Zou, S. Xin, X. Zeng and S. Chen for technical assistance. Supported by the Ministry of Science and Technology (2005CB522406 and 2009CB941100), the National Natural Science Foundation of China (30621091, 30625014, 30623003, 30871285, 90713047 and 90919028), the Shanghai Municipal Commission for Science and Technology (07PJ14099) and the Chinese Academy of Sciences (2007KIP204 and SIBS2008001).

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  1. Changsheng Du and Chang Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    Changsheng Du, Chang Liu, Jiuhong Kang, Shichao Huang & Gang Pei

  2. School of Life Science and Technology, Tongji University, Shanghai, China

    Jiuhong Kang & Gang Pei

  3. Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Shanghai, China

    Guixian Zhao, Zhenxin Li & Zhiying Wu

  4. Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    Zhiqiang Ye

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Contributions

C.D., C.L., J.K. and G.P. designed the study; C.D., C.L. and S.H. did the experiments; Z.Y. contributed to the bioinformatics analysis target prediction; Z.W., Z.L. and G.Z. provided clinical samples; G.P. supervised the project; and C.L., C.D. and J.K. contributed to the writing of the paper.

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Correspondence to Gang Pei.

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Du, C., Liu, C., Kang, J. et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10, 1252–1259 (2009). https://doi.org/10.1038/ni.1798

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