MiR-15a contributes abnormal immune response in myasthenia gravis by targeting CXCL10
Xiao-Fang Liu1, Run-Qi Wang2, Bo Hu1
1Department of Neurology, Xiangya Hospital, Central South University, People's Republic of China.
Abstract:
MiR-15a is likely to be associated with autoimmunity. Here, we aimed to examine the expression of miR-15 cluster in PBMCs from myasthenia gravis (MG) patients and investigate the potential roles of miR-15a in MG. We found that the expression of all miR-15 cluster was decreased in MG, furthermore, miR-15a levels in ocular MG (oMG) were much lower, while CXCL10 production was increased in MG. We display that CXCL10 was a functional target gene of miR-15a in MG. Increasing miR-15a expression could reduce CXCL10 expression and alleviate the abnormal T cells activation in immune response, while decreasing miR-15a expression could activate immune response abnormally. Moreover, miR-15a expression was significantly decreased after stimulation, and prednisone treatment could upregulate miR-15a expression in steroid-responsive MG patients. Take together, our data suggest that decreased miR-15a expression facilitates proinflammatory cytokines production and contributes to immune response at least in part via regulating CXCL10 expression in MG.
Insights
Decreased miR-15a expression in myasthenia gravis (MG) patients correlates with increased CXCL10, suggesting miR-15a regulates immune responses. Prednisone may restore miR-15a levels in some patients.
Area of Science:
- Immunology
- Molecular Biology
- Neuroimmunology
Background:
- Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions.
- MicroRNAs (miRNAs) play crucial roles in regulating immune responses and are implicated in autoimmunity.
- The miR-15 cluster, including miR-15a, is a potential candidate for investigation in MG pathogenesis.
Purpose of the Study:
- To investigate the expression levels of the miR-15 cluster in peripheral blood mononuclear cells (PBMCs) from MG patients.
- To explore the functional role of miR-15a in the context of MG, particularly its relationship with CXCL10.
- To assess the impact of disease state and treatment on miR-15a expression in MG.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure miR-15 cluster expression in PBMCs.
- Analysis of CXCL10 levels in MG patients.
- Functional assays to determine the regulatory relationship between miR-15a and CXCL10.
- Assessment of T cell activation markers.
- Evaluation of miR-15a expression post-stimulation and after prednisone treatment.
Main Results:
- All members of the miR-15 cluster showed decreased expression in MG patients compared to controls.
- miR-15a levels were significantly lower in ocular MG (oMG) patients.
- CXCL10 production was elevated in MG patients, and it was identified as a direct target of miR-15a.
- Upregulating miR-15a reduced CXCL10 expression and mitigated abnormal T cell activation.
- Prednisone treatment increased miR-15a expression in steroid-responsive MG patients.
Conclusions:
- Decreased miR-15a expression contributes to the pathogenesis of MG by promoting pro-inflammatory cytokine production, at least partly through regulating CXCL10.
- miR-15a acts as a negative regulator of immune responses in MG.
- Restoration of miR-15a levels by prednisone may be a therapeutic mechanism in steroid-responsive MG.
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