Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis

G Murugaiyan, V Beynon, A Mittal, N Joller… - The Journal of …, 2011 - journals.aai.org
G Murugaiyan, V Beynon, A Mittal, N Joller, HL Weiner
The Journal of Immunology, 2011journals.aai.org
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) …
Abstract
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.
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