IFN-γ–producing Th1 and IL-17–producing Th17 cells are the key participants in various autoimmune diseases, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Although both of these T cell subsets are known to be regulated by specific transcription factors and cytokines, the role of microRNAs that control these two inflammatory T cell subsets and whether targeting microRNAs can have therapeutic effects are not known. In this study, we show that microRNA-155 (Mir-155) expression is elevated in CD4+ T cells during EAE, and Mir-155−/− mice had a delayed course and reduced severity of disease and less inflammation in the CNS. The attenuation of EAE in Mir-155−/− mice was associated with a decrease in Th1 and Th17 responses in the CNS and peripheral lymphoid organs. The T cell-intrinsic function of Mir-155−/− was demonstrated by the resistance of Mir-155−/− CD4+ T cell-repleted Rag-1−/− mice to EAE. Finally, we found that anti–Mir-155 treatment reduced clinical severity of EAE when given before and after the appearance of clinical symptoms. These findings demonstrate that Mir-155 confers susceptibility to EAE by affecting inflammatory T cell responses and identify Mir-155 as a new target for therapeutic intervention in multiple sclerosis.
See Winger and Zamvil (doi:
) for a scientific commentary on this article.
Current therapies have limited effect on the chronic CNS inflammation observed in progressive multiple sclerosis (MS). Mayo
et al.
show that CD3-specific antibody ameliorates disease in a mouse model of progressive MS. The effect is dependent on induction of regulatory T-cells, which attenuate astrocyte and microglia activation via secretion of interleukin-10.
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