Journal Article

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

Ye, Zhiqiang, Huang, Shichao, Wu, Zhiying, Pei, Gang, Kang, Jiuhong, Zhao, Guixian, Li, Zhenxin, Du, Changsheng, Liu, Chang

2009

Overview

Interleukin 17 (IL-17)-producing helper T cells (T H -17 cells) are associated with the pathogenesis of multiple sclerosis. Pei and colleagues have now identified a T H -17 cell–associated microRNA, miR-326, whose expression correlates with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis. Interleukin 17 (IL-17)-producing T helper cells (T H -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 T H -17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a T H -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 T H -17 cells and mild EAE, and its overexpression led to more T H -17 cells and severe EAE. We also found that miR-326 promoted T H -17 differentiation by targeting Ets-1, a negative regulator of T H -17 differentiation. Our data show a critical role for microRNA in T H -17 differentiation and the pathogenesis of multiple sclerosis.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Adult / Animals / Autoimmune diseases / Base Sequence / Biomedical and Life Sciences / Biomedicine / Cell Differentiation / Encephalomyelitis, Autoimmune, Experimental - genetics / Encephalomyelitis, Autoimmune, Experimental - immunology / Encephalomyelitis, Autoimmune, Experimental - metabolism / Encephalomyelitis, Autoimmune, Experimental - pathology / Female / Humans / Immunology / Infectious Diseases / Interleukin-17 - immunology / Male / Mice / MicroRNAs - genetics / Multiple Sclerosis - genetics / Multiple Sclerosis - immunology / Multiple Sclerosis - pathology / Proto-Oncogene Protein c-ets-1 - genetics / Proto-Oncogene Protein c-ets-1 - metabolism / T-Lymphocytes, Helper-Inducer - cytology / T-Lymphocytes, Helper-Inducer - immunology / T-Lymphocytes, Helper-Inducer - metabolism / Up-Regulation