MicroRNA-155 modulates Th1 and Th17 cell differentiation and is associated with multiple sclerosis and experimental
Jing Zhang1, Ye Cheng1, Wei Cui1
1The Department of Neurology of the Second Hospital of Hebei Medical University, China.
Abstract:
Mammalian noncoding microRNAs (miRNAs) are suggested to be involved in immune system function. We found that miR-155 expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). Knockdown of miR-155 resulted in low Th1 and Th17 cells and mild EAE, and its overexpression led to more Th1 and Th17 cells and severe EAE. MiR-155 promoted the development of inflammatory Th17/Th1 cell subsets. These findings demonstrate that miR-155 confers susceptibility to EAE by affecting inflammatory T cell responses and can be a new target for therapy of multiple sclerosis.
Insights
MicroRNA-155 (miR-155) drives autoimmune disease severity in multiple sclerosis and experimental autoimmune encephalomyelitis by promoting inflammatory T cell responses. Reducing miR-155 may offer a novel therapeutic strategy for these conditions.
Area of Science:
- Immunology
- Molecular Biology
- Neuroscience
Background:
- Noncoding microRNAs (miRNAs) play a role in immune system regulation.
- Dysregulation of miRNAs is implicated in autoimmune diseases like multiple sclerosis (MS).
Purpose of the Study:
- To investigate the role of microRNA-155 (miR-155) in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE).
- To determine if miR-155 can be a therapeutic target for MS.
Main Methods:
- Correlative analysis of miR-155 expression with disease severity in MS patients and EAE mice.
- In vivo knockdown and overexpression of miR-155 in EAE mouse models.
- Analysis of T helper cell subsets (Th1 and Th17) and their inflammatory profiles.
Main Results:
- miR-155 expression levels strongly correlated with disease severity in both MS patients and EAE mice.
- Knockdown of miR-155 led to reduced Th1 and Th17 cells and attenuated EAE.
- Overexpression of miR-155 resulted in increased Th1 and Th17 cells and exacerbated EAE.
- miR-155 was found to promote the development of inflammatory Th17/Th1 cell subsets.
Conclusions:
- miR-155 significantly contributes to susceptibility to EAE by modulating inflammatory T cell responses.
- miR-155 represents a potential therapeutic target for multiple sclerosis and related autoimmune conditions.
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