PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity.
PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity.
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DOI：
10.3389/fimmu.2021.695947
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发表时间：
2021
影响因子：
7.3
通讯作者：
Guerau-de-Arellano M
中科院分区：
文献类型：
--
作者：
Amici SA;Osman W;Guerau-de-Arellano M
多发性硬化症（MS）是一种与炎性T细胞相关的使人衰弱的中枢神经系统疾病。炎症性T细胞的激活和扩增被认为是MS复发的原因，并影响疾病的严重程度。蛋白质精氨酸N-甲基转移酶5（PRMT 5）是T细胞活化诱导的酶，其对称地二甲基化蛋白质并促进T细胞增殖。然而，PRMT 5介导的T细胞增殖控制背后的机制以及PRMT 5是否有助于疾病的严重程度尚不清楚。在此，我们评估了PRMT 5对细胞周期蛋白/cdk对和细胞周期进程的作用，以及PRMT 5与复发缓解型MS动物模型中疾病严重程度的联系。用选择性PRMT 5抑制剂HLCL 65处理辅助性T细胞1（mTh 1）细胞，将活化诱导的T细胞增殖阻滞在细胞周期的G1期，提示PRMT 5促进CD 4 + T细胞中的细胞周期进程。PRMT 5抑制后，促进G1/S进程的细胞周期蛋白E1/Cdk 2对也减少，视网膜母细胞瘤的磷酸化也是如此。在MS的SJL小鼠复发-缓解模型中，中枢神经系统浸润细胞中的最高PRMT 5表达对应于峰值和复发时间点。PRMT 5表达与CD 4 Th细胞组成、疾病严重程度和Cyclin E1表达呈正相关。这些数据表明PRMT 5促进G1/S细胞周期进展，并表明这种作用影响MS动物模型中的疾病严重程度和/或进展。调节PRMT 5水平可用于控制T细胞介导的疾病（包括MS）中的T细胞扩增。
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.
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DOI：
10.1042/bj20120768
发表时间：
2012-09-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Gu Z;Gao S;Zhang F;Wang Z;Ma W;Davis RE;Wang Z
通讯作者：
Wang Z
影响因子：
14.9
作者：
Scoumanne A;Zhang J;Chen X
通讯作者：
Chen X
影响因子：
4.4
作者：
Okuda, Y;Okuda, M;Posnett, DN
通讯作者：
Posnett, DN
影响因子：
4
作者：
Bedford, Mark T.
通讯作者：
Bedford, Mark T.
影响因子：
--
作者：
Khoury, SJ;Guttmann, CRG;Weiner, HL
通讯作者：
Weiner, HL