MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis (Nat Immunol, 2009, 10:1252-1259)

報告日期: 2010/04/27
報告時間: 16:10/18:00
報告學生: 呂佳馨
講評老師: 張明熙
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990427-3.pdf

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

Du et al. Nature medicine 10, 1252-1259, 2009

 

Speaker: Chia-Hsing Leu

Commentator: Dr. Ming-Shi Chang

Time: 16:00~16:50, 4/27/2010

Room: 602

 

Abstact:

Interleukin 17 (IL-17)-producing T cells (TH-17 cells) have recently been identified as a new lineage of effector TH cells and are critically involved in various autoimmune diseases, including multiple sclerosis. TH-17 differentiation is affected by transcription factors and polarizing cytokines. MicroRNAs represent a large family of endogenous noncoding RNAs that are thought to functionally target multiple proteins and participate in most biologic processes. However, the role of microRNAs in the regulation and control of autoimmune disease is not clear. In this study, the authors found that miR-326 is highly expressed in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). They designed lentiviral vectors encoding pre-miR-326 (LV-326), a mutant miR326 control (LV-ctrl) or its specific inhibitor (LV-sponge). The LV-326-infected mice developed prominent inflammatory infiltration and demyelination, whereas LV-sponge-infected mice had mild EAE. TH-17 generation was more evident in LV-326-infected mice than in LV-sponge-infected mice. Furthermore, microRNA inhibitor LNA-anti-miR326 produced an inhibitory effect on TH-17 differentiation similar to that of infection with LV-sponge. Thus, miR-326 in TH-17 might be correlated with disease severity. Finally, they demonstrated that the differentiation of TH-17 cells regulated by miR-326 is mainly through targeting Ets-1, a negative regulator of TH-17. Collectively, these findings reveal that miR-326 is a TH-17-associated microRNA in TH-17 differentiation and the pathogenesis of multiple sclerosis. They may provide a new target for clinical application in multiple sclerosis.

 

References:

1. Korn, T., Bettelli, E., Oukka, M. & Kuchroo, V.K. IL-17 and Th17 cells. Annu. Rev. Immunol. 27, 485–517 (2009).

2. Bartel, D.P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009).