Niu Xinli, Liu Zejin, Wang Junpeng, Wu Dayong
Translational Medical Center, Huaihe Hospital of Henan University, Kaifeng, 475000, China.
College of Life Science, Henan University, Kaifeng, 475000, China.
Curr Res Food Sci. 2023 Jun 18;7:100537. doi: 10.1016/j.crfs.2023.100537. eCollection 2023.
Dietary green tea epigallocatechin-3-gallate (EGCG) could attenuate experimental autoimmune encephalomyelitis via the modification of the balance of CD4 T helper (Th) cells. Moreover, EGCG administration has a direct impact on the regulatory cytokines and differentiation of CD4 T cells. Here, we aim to determine whether EGCG directly affects the cell division and progression in naive CD4 T cells. We first investigate the effect of EGCG on naïve CD4 T cell division and progression . An integrated analysis of network pharmacology and molecular docking was utilized to further identify the targets of EGCG for T cell-mediated autoimmune diseases and multiple sclerosis (MS). EGCG treatment prevented naïve CD4 T cells from progressing through the cell cycle when stimulated with anti-CD3/CD28 antibodies. This was achieved by increasing the proportion of cells arrested in the G0/G1 phase by 8.6% and reducing DNA synthesis activity by 51% in the S phase. Furthermore, EGCG treatment inhibited the expression of cyclins (cyclin D1, cyclin D3, cyclin A, and cyclin B1) and CDKs (CDK2 and CDK6) during naïve CD4 T cell activation in response to anti-CD3/CD28 stimulation. However, EGCG inhibited the decrease of P27 (CDKN1B) during naïve CD4 T cell activation, whereas it inhibited the increase of P21 (CDKN1A) expression 48 h after mitogenic stimulation. The molecular docking analysis confirmed that these proteins (CD4, CCND1, and CDKN1A) are the primary targets for EGCG, T cell-mediated autoimmune diseases, and MS. Finally, target enrichment analysis indicated that EGCG may affect the cell cycle, T cell receptor signaling pathway, Th cell differentiation, and NF-κB signaling pathway. These findings reveal a crucial role of EGCG in the division and progression of CD4 T cells, and underscore other potential targets of EGCG in T cell-mediated autoimmune diseases such as MS.
膳食中的绿茶表没食子儿茶素-3-没食子酸酯（EGCG）可通过调节CD4辅助性T（Th）细胞的平衡来减轻实验性自身免疫性脑脊髓炎。此外，给予EGCG对调节性细胞因子和CD4 T细胞的分化有直接影响。在此，我们旨在确定EGCG是否直接影响初始CD4 T细胞的细胞分裂和进程。我们首先研究EGCG对初始CD4 T细胞分裂和进程的影响。利用网络药理学和分子对接的综合分析来进一步确定EGCG在T细胞介导的自身免疫性疾病和多发性硬化症（MS）中的靶点。当用抗CD3/CD28抗体刺激时，EGCG处理可阻止初始CD4 T细胞通过细胞周期。这是通过将停滞在G0/G1期的细胞比例提高8.6%以及将S期的DNA合成活性降低51%来实现的。此外，在抗CD3/CD28刺激下初始CD4 T细胞活化期间，EGCG处理抑制了细胞周期蛋白（细胞周期蛋白D1、细胞周期蛋白D3、细胞周期蛋白A和细胞周期蛋白B1）和细胞周期蛋白依赖性激酶（CDK2和CDK6）的表达。然而，EGCG在初始CD4 T细胞活化期间抑制了P27（CDKN1B）的减少，而在有丝分裂原刺激48小时后它抑制了P21（CDKN1A）表达的增加。分子对接分析证实这些蛋白质（CD4、CCND1和CDKN1A）是EGCG、T细胞介导的自身免疫性疾病和MS的主要靶点。最后，靶点富集分析表明EGCG可能影响细胞周期、T细胞受体信号通路、Th细胞分化和NF-κB信号通路。这些发现揭示了EGCG在CD4 T细胞的分裂和进程中的关键作用，并强调了EGCG在T细胞介导的自身免疫性疾病如MS中的其他潜在靶点。
