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Published online: 28 October 2009 | doi:10.1038/nchina.2009.208

Immunology: Decoding multiple sclerosis

Felix Cheung

Introduction

© (2009) istockphoto.com/Dennis Hoyne

Interleukin 17-producing T helper cells (T_H-17 cells) play an important role in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) — one of the foremost causes of neurological disability in young adults. Gang Pei at the Chinese Academy of Sciences in Shanghai and co-workers¹ have identified a microRNA involved in the differentiation of T_H-17 cells and the regulation and control of MS. The microRNA, known as miR-326, may one day serve as a diagnostic marker and therapeutic target for the disease.

The researchers found that miR-326 expression was significantly higher in peripheral blood cells of patients with MS than in those of patients with neuromyelitis optica, an inflammatory demyelinating disease that is often misdiagnosed as MS because of closely similar symptoms. Detailed analysis showed that the miR-326 expression level is highly correlated with disease severity in MS patients.

The researchers then sought to determine the link between miR-326 and T_H-17 cells. They used viral vectors to deliver the microRNA into mice with experimental autoimmune encephalomyelitis (EAE), the common animal model that mirrors many hallmarks of MS. Silencing of miR-326 resulted in fewer T_H-17 cells and mild EAE, whereas overexpression of miR-326 led to more T_H-17 cells and severe EAE.

The researchers also found that miR-326 promoted T_H-17 differentiation by targeting Ets-1, a negative regulator of T_H-17 differentiation. The findings reveal the critical role of microRNA in T_H-17 differentiation and the pathogenesis of MS.

The authors of this work are from:
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; School of Life Science and Technology, Tongji University, Shanghai, China; Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Shanghai, China; Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Reference

1. Du, C. et al. MicroRNA miR-326 regulates T_H-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nature Immunol. doi:10.1038/ni.1798 (2009). | Article | OpenURL