Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis

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 fa...

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Published in:The Journal of immunology (1950) Vol. 187; no. 5; p. 2213
Main Authors: Murugaiyan, Gopal, Beynon, Vanessa, Mittal, Akanksha, Joller, Nicole, Weiner, Howard L
Format: Journal Article
Language:English
Published: England 01.09.2011
Subjects:
Animals
CD4-Positive T-Lymphocytes - immunology
Encephalomyelitis, Autoimmune, Experimental - genetics
Encephalomyelitis, Autoimmune, Experimental - immunology
Gene Silencing
Inflammation - genetics
Inflammation - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs - genetics
MicroRNAs - immunology
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocyte Subsets - immunology
ISSN:1550-6606, 1550-6606
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Summary: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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ISSN:1550-6606
1550-6606
DOI:10.4049/jimmunol.1003952