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IFNA-AS1 regulates CD4+ T cell activation in myasthenia gravis though HLA-DRB1
Mengchuan Luo1, Xiaofang Liu1, Huanyu Meng1
1Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Neurology Institute of Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Insights
The long non-coding RNA IFNG-AS1 is abnormally expressed in myasthenia gravis (MG) patients. This lncRNA influences T cell subsets and immune responses, suggesting a role in MG pathogenesis.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Abnormal CD4+ T cell activation is implicated in myasthenia gravis (MG) pathogenesis.
- The role of long non-coding RNAs (lncRNAs) in regulating CD4+ T cells in MG remains largely unknown.
Purpose of the Study:
- To investigate the expression and function of lncRNAs, specifically IFNG-AS1, in CD4+ T cells within the context of myasthenia gravis.
- To elucidate the mechanisms by which IFNG-AS1 influences T cell subsets and immune responses in MG.
Main Methods:
- Quantitative real-time PCR to assess IFNG-AS1 expression in MG patients.
- In vitro studies using an experimental autoimmune myasthenia gravis (EAMG) model to evaluate IFNG-AS1's impact on Th1 and Treg cell proliferation and transcription factors.
- Analysis of HLA-DRB and HLA-DOB expression, and CD40L and CD4+ T cell activation in MG patients.
Main Results:
- IFNG-AS1 was found to be abnormally expressed in MG patients, correlating with quantitative MG scores and anti-AchR antibody levels.
- IFNG-AS1 influenced Th1/Treg cell proliferation and regulated their transcription factors in an EAMG model.
- IFNG-AS1 reduced HLA-DRB and HLA-DOB expression, showing a negative correlation in MG.
- IFNG-AS1 affected CD40L expression and CD4+ T cell activation in MG patients, partly via HLA-DRB1.
Conclusions:
- IFNG-AS1 is abnormally expressed in myasthenia gravis.
- IFNG-AS1 plays a role in regulating CD4+ T cell subsets and immune responses in MG.
- IFNG-AS1 may be a potential therapeutic target for CD4+ T cell-mediated immune responses in MG.
Abstract:
Abnormal CD4+T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4+ T cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. IFNG-AS1 influenced Th1/Treg cell proliferation and regulated the expression levels of their transcription factors in an experimental autoimmune myasthenia gravis (EAMG)model. IFNG-AS1 could reduce the expression of HLA-DRB and HLA-DOB and they had a negative correlation in MG. Furthermore IFNG-AS1 influenced the expression levels of CD40L and CD4+ T cells activation in MG patient partly depend on effecting the HLA-DRB1 expression. It suggests that IFNG-AS1 may be involved in CD4+T cell-mediated immune responses in MG.
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