PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity
Multiple Sclerosis (MS) is a debilitating central nervous system disorder associated with inflammatory T cells. Activation and expansion of inflammatory T cells is thought to be behind MS relapses and influence disease severity. Protein arginine N-methyltransferase 5 (PRMT5) is a T cell activation-i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.695947/full |
| _version_ | 1818573794105622528 |
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| author | Stephanie A. Amici Wissam Osman Mireia Guerau-de-Arellano Mireia Guerau-de-Arellano Mireia Guerau-de-Arellano Mireia Guerau-de-Arellano |
| author_facet | Stephanie A. Amici Wissam Osman Mireia Guerau-de-Arellano Mireia Guerau-de-Arellano Mireia Guerau-de-Arellano Mireia Guerau-de-Arellano |
| author_sort | Stephanie A. Amici |
| collection | DOAJ |
| description | Multiple Sclerosis (MS) is a debilitating central nervous system disorder associated with inflammatory T cells. Activation and expansion of inflammatory T cells is thought to be behind MS relapses and influence disease severity. Protein arginine N-methyltransferase 5 (PRMT5) is a T cell activation-induced enzyme that symmetrically dimethylates proteins and promotes T cell proliferation. However, the mechanism behind PRMT5-mediated control of T cell proliferation and whether PRMT5 contributes to diseases severity is unclear. Here, we evaluated the role of PRMT5 on cyclin/cdk pairs and cell cycle progression, as well as PRMT5’s link to disease severity in an animal model of relapsing-remitting MS. Treatment of T helper 1 (mTh1) cells with the selective PRMT5 inhibitor, HLCL65, arrested activation-induced T cell proliferation at the G1 stage of the cell cycle, suggesting PRMT5 promotes cell cycle progression in CD4+ T cells. The Cyclin E1/Cdk2 pair promoting G1/S progression was also decreased after PRMT5 inhibition, as was the phosphorylation of retinoblastoma. In the SJL mouse relapsing-remitting model of MS, the highest PRMT5 expression in central nervous system-infiltrating cells corresponded to peak and relapse timepoints. PRMT5 expression also positively correlated with increasing CD4 Th cell composition, disease severity and Cyclin E1 expression. These data indicate that PRMT5 promotes G1/S cell cycle progression and suggest that this effect influences disease severity and/or progression in the animal model of MS. Modulating PRMT5 levels may be useful for controlling T cell expansion in T cell-mediated diseases including MS. |
| first_indexed | 2024-12-15T00:17:39Z |
| format | Article |
| id | doaj.art-5f71508ff53e43b5b18d587c00503c83 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-15T00:17:39Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5f71508ff53e43b5b18d587c00503c832022-12-21T22:42:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.695947695947PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE SeverityStephanie A. Amici0Wissam Osman1Mireia Guerau-de-Arellano2Mireia Guerau-de-Arellano3Mireia Guerau-de-Arellano4Mireia Guerau-de-Arellano5School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, United StatesDiscovery PREP Program, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, United StatesSchool of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, United StatesInstitute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, United StatesDepartment of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United StatesDepartment of Neuroscience, The Ohio State University, Columbus, OH, United StatesMultiple Sclerosis (MS) is a debilitating central nervous system disorder associated with inflammatory T cells. Activation and expansion of inflammatory T cells is thought to be behind MS relapses and influence disease severity. Protein arginine N-methyltransferase 5 (PRMT5) is a T cell activation-induced enzyme that symmetrically dimethylates proteins and promotes T cell proliferation. However, the mechanism behind PRMT5-mediated control of T cell proliferation and whether PRMT5 contributes to diseases severity is unclear. Here, we evaluated the role of PRMT5 on cyclin/cdk pairs and cell cycle progression, as well as PRMT5’s link to disease severity in an animal model of relapsing-remitting MS. Treatment of T helper 1 (mTh1) cells with the selective PRMT5 inhibitor, HLCL65, arrested activation-induced T cell proliferation at the G1 stage of the cell cycle, suggesting PRMT5 promotes cell cycle progression in CD4+ T cells. The Cyclin E1/Cdk2 pair promoting G1/S progression was also decreased after PRMT5 inhibition, as was the phosphorylation of retinoblastoma. In the SJL mouse relapsing-remitting model of MS, the highest PRMT5 expression in central nervous system-infiltrating cells corresponded to peak and relapse timepoints. PRMT5 expression also positively correlated with increasing CD4 Th cell composition, disease severity and Cyclin E1 expression. These data indicate that PRMT5 promotes G1/S cell cycle progression and suggest that this effect influences disease severity and/or progression in the animal model of MS. Modulating PRMT5 levels may be useful for controlling T cell expansion in T cell-mediated diseases including MS.https://www.frontiersin.org/articles/10.3389/fimmu.2021.695947/fullPRMT5cell cyclerelapsing-remitting experimental autoimmune encephalomyelitisT cellmultiple sclerosis |
| spellingShingle | Stephanie A. Amici Wissam Osman Mireia Guerau-de-Arellano Mireia Guerau-de-Arellano Mireia Guerau-de-Arellano Mireia Guerau-de-Arellano PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity Frontiers in Immunology PRMT5 cell cycle relapsing-remitting experimental autoimmune encephalomyelitis T cell multiple sclerosis |
| title | PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity |
| title_full | PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity |
| title_fullStr | PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity |
| title_full_unstemmed | PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity |
| title_short | PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity |
| title_sort | prmt5 promotes cyclin e1 and cell cycle progression in cd4 th1 cells and correlates with eae severity |
| topic | PRMT5 cell cycle relapsing-remitting experimental autoimmune encephalomyelitis T cell multiple sclerosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.695947/full |
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