Autoreactive CD4 T cells that differentiate into pathogenic Th17 cells can trigger autoimmune diseases. Therefore, investigating the regulatory network that modulates Th17 differentiation may yield important therapeutic insights. miR-146a has emerged as a critical modulator of immune reactions, but its role in regulating autoreactive Th17 cells and organ-specific autoimmunity remains largely unknown. Here, we have reported that miR-146a–deficient mice developed more severe experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). We bred miR-146a–deficient mice with 2D2 T cell receptor–Tg mice to generate 2D2 CD4 T cells that are deficient in miR-146a and specific for myelin oligodendrocyte glycoprotein (MOG), an autoantigen in the EAE model. miR-146a–deficient 2D2 T cells induced more severe EAE and were more prone to differentiate into Th17 cells. Microarray analysis revealed enhancements in IL-6– and IL-21–induced Th17 differentiation pathways in these T cells. Further study showed that miR-146a inhibited the production of autocrine IL-6 and IL-21 in 2D2 T cells, which in turn reduced their Th17 differentiation. Thus, our study identifies miR-146a as an important molecular brake that blocks the autocrine IL-6– and IL-21–induced Th17 differentiation pathways in autoreactive CD4 T cells, highlighting its potential as a therapeutic target for treating autoimmune diseases.
Bo Li, Xi Wang, In Young Choi, Yu-Chen Wang, Siyuan Liu, Alexander T. Pham, Heesung Moon, Drake J. Smith, Dinesh S. Rao, Mark P. Boldin, Lili Yang
Title and authors | Publication | Year |
---|---|---|
MiRNA-210 induces microglial activation and regulates microglia-mediated neuroinflammation in neonatal hypoxic-ischemic encephalopathy
B Li, C Dasgupta, L Huang, X Meng, L Zhang |
Cellular and Molecular Immunology | 2019 |
The PARP inhibitor olaparib exerts beneficial effects in mice subjected to cecal ligature and puncture and in cells subjected to oxidative stress without impairing DNA integrity: A potential opportunity for repurposing a clinically used oncological drug for the experimental therapy of sepsis
A Ahmad, J de Camargo Vieira, AH de Mello, TM de Lima, SK Ariga, DF Barbeiro, HV Barbeiro, B Szczesny, G Törö, N Druzhyna, EB Randi, M Marcatti, T Toliver-Kinsky, A Kiss, L Liaudet, R Salomao, FG Soriano, C Szabo |
Pharmacological research : the official journal of the Italian Pharmacological Society | 2019 |
Let-7f-5p suppresses Th17 differentiation via targeting STAT3 in multiple sclerosis
ZH Li, YF Wang, DD He, XM Zhang, YL Zhou, H Yue, S Huang, Z Fu, LY Zhang, ZQ Mao, S Li, CY Zhang, , J Fu |
Aging | 2019 |
Multiple roles of microRNA‑146a in immune responses and hepatocellular carcinoma (Review)
H Wang, X Li, T Li, L Wang, X Wu, J Liu, Y Xu, W Wei |
Oncology Letters | 2019 |
Intranasal Administration of miR-146a Agomir Rescued the Pathological Process and Cognitive Impairment in an AD Mouse Model
H Mai, W Fan, Y Wang, Y Cai, X Li, F Chen, X Chen, J Yang, P Tang, H Chen, T Zou, T Hong, C Wan, B Zhao, L Cui |
Molecular Therapy — Nucleic Acids | 2019 |
Creatine uptake regulates CD8 T cell antitumor immunity
SD Biase, X Ma, , J Yu, YC Wang, DJ Smith, Y Zhou, Z Li, YJ Kim, N Clarke, A To, L Yang |
Journal of Experimental Medicine | 2019 |