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PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity
Stephanie A Amici1, Wissam Osman2, Mireia Guerau-de-Arellano1,3,4,5
1School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, United States.
Frontiers in Immunology
|June 25, 2021
Summary
Protein arginine N-methyltransferase 5 (PRMT5) drives T cell proliferation and disease severity in Multiple Sclerosis (MS). Inhibiting PRMT5 halts T cell cycle progression, offering a potential therapeutic strategy for MS and other T cell-mediated diseases.
Area of Science:
- Neuroimmunology
- Cell Biology
- Molecular Medicine
Background:
- Multiple Sclerosis (MS) involves inflammatory T cells, with their expansion linked to disease relapses and severity.
- Protein arginine N-methyltransferase 5 (PRMT5) is an enzyme induced during T cell activation, promoting proliferation, but its precise role in MS is unclear.
Purpose of the Study:
- To investigate the mechanism of PRMT5 in T cell proliferation and its contribution to MS disease severity.
- To evaluate PRMT5's effect on cell cycle progression and its correlation with disease markers in a mouse model of MS.
Main Methods:
- Treatment of T helper 1 (mTh1) cells with a selective PRMT5 inhibitor (HLCL65) to assess cell cycle progression.
- Analysis of PRMT5 expression in CNS-infiltrating cells during different stages of experimental autoimmune encephalomyelitis (EAE) in SJL mice.
- Correlation of PRMT5 expression with CD4+ T cell composition, disease severity, and cell cycle markers.
Main Results:
- PRMT5 inhibition arrested T cell proliferation at the G1 stage, indicating PRMT5 promotes cell cycle progression.
- PRMT5 inhibition reduced levels of Cyclin E1/Cdk2 and phosphorylated retinoblastoma, key regulators of G1/S phase transition.
- In the MS mouse model, peak PRMT5 expression coincided with disease relapses, and its expression positively correlated with disease severity and CD4+ T cell infiltration.
Conclusions:
- PRMT5 promotes G1/S cell cycle progression in T cells, contributing to disease severity in an MS model.
- Targeting PRMT5 may represent a viable therapeutic approach for managing T cell expansion in MS and related inflammatory diseases.
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