MicroRNA 182 inhibits CD4+CD25+Foxp3+ Treg differentiation in experimental autoimmune encephalomyelitis
Cong Wan1, Chang-Yun Ping2, Xiao-Yu Shang3
1Department of Neurobiology, Harbin Medical University, No.194 XueFu Road, Harbin, Heilongjiang 150081, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Provence 150086, China.
Abstract:
MicroRNA 182 has been found to have a distinct contribution in the clonal expansion of activated- and functioning of specialized-helper T cells. In this study we knocked down microRNA 182 in vivo and induced experimental autoimmune encephalomyelitis (EAE) to determine the influences of microRNA 182 in the Treg cells functional specialization through Foxo1 dependent pathway in the peripheral lymphoid organs. Down-regulation of microRNA 182 significantly increased the proportions of Foxp3+ T cells in the peripheral lymph nodes and spleen. In vivo study verified a positive correlation between microRNA 182 levels and symptom severity of EAE, and a negative correlation between microRNA 182 and the transcriptional factor Foxp3. In vitro polarization study also confirmed the contribution of Foxo1 in microRNA 182 mediated down-regulation of Foxp3+ T cells. Together, our results provide evidence that during the development of EAE, microRNA 182 repressed Treg cells differentiation through the Foxo1 dependent pathway.
Insights
MicroRNA 182 (miR-182) represses regulatory T (Treg) cell differentiation in experimental autoimmune encephalomyelitis (EAE) by inhibiting the Foxo1 pathway. Lowering miR-182 boosts Treg cell numbers and function, mitigating EAE severity.
Area of Science:
- Immunology
- Molecular Biology
- Neuroscience
Background:
- MicroRNA 182 (miR-182) plays a role in T cell clonal expansion.
- Regulatory T (Treg) cells are crucial for immune homeostasis and preventing autoimmunity.
- Experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis.
Purpose of the Study:
- To investigate the role of miR-182 in Treg cell functional specialization during EAE.
- To elucidate the involvement of the Foxo1-dependent pathway in miR-182's effects on Treg cells.
Main Methods:
- In vivo knockdown of miR-182 in a mouse model of EAE.
- Analysis of Treg cell populations (Foxp3+) in peripheral lymphoid organs.
- In vitro Treg cell polarization assays.
- Correlation analysis between miR-182 levels, EAE severity, and Foxp3 expression.
Main Results:
- Down-regulation of miR-182 significantly increased Foxp3+ T cell proportions in lymph nodes and spleen.
- A positive correlation was observed between miR-182 levels and EAE symptom severity.
- A negative correlation was found between miR-182 levels and the transcription factor Foxp3.
- In vitro studies confirmed Foxo1's role in miR-182-mediated suppression of Foxp3+ T cells.
Conclusions:
- MicroRNA 182 represses Treg cell differentiation during EAE development.
- This repression occurs via a Foxo1-dependent pathway.
- Modulating miR-182 levels may offer a therapeutic strategy for autoimmune diseases like EAE.
