Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China.
Front Immunol. 2020 Oct 8;11:575669. doi: 10.3389/fimmu.2020.575669. eCollection 2020.
Experimental autoimmune uveitis (EAU) is a CD4 T cell-mediated organ-specific autoimmune disease and has been considered as a model of human autoimmune uveitis. (DH) is a Chinese herbal medicine used in treating hepatitis. DH suppressed the production of inflammatory cytokines through the recruitment of myeloid-derived suppressor cells (MDSCs) to the liver. However, it remains elusive whether DH can directly regulate CD4 T cell biology and hence ameliorates the development of CD4 T cell-mediated autoimmune disease. In the current study, we found that DH extract significantly suppressed the production of pro-inflammatory cytokines by CD4 T cells. Further study showed that DH didn't affect the activation, differentiation, and apoptosis of CD4 T cells. Instead, it significantly suppressed the proliferation of conventional CD4 T cells both and . Mechanistic study showed that DH-treated CD4 T cells were partially arrested at the G2/M phase of the cell cycle because of the enhanced inhibitory phosphorylation of Cdc2 (Tyr15). In addition, we demonstrated that treatment with DH significantly ameliorated EAU in mice through suppressing the proliferation of autoreactive antigen specific CD4 T cells. Taken together, the current study indicates that DH-mediated suppression of CD4 T cell proliferation may provide a promising therapeutic strategy for treating CD4 T cell-mediated diseases.
实验性自身免疫性葡萄膜炎(EAU)是一种 CD4 T 细胞介导的器官特异性自身免疫性疾病,已被认为是人类自身免疫性葡萄膜炎的模型。DH 是一种用于治疗肝炎的中药。DH 通过募集髓系来源的抑制细胞(MDSCs)到肝脏来抑制炎症细胞因子的产生。然而,DH 是否能直接调节 CD4 T 细胞的生物学功能,从而改善 CD4 T 细胞介导的自身免疫性疾病的发展,仍不清楚。在本研究中,我们发现 DH 提取物能显著抑制 CD4 T 细胞产生促炎细胞因子。进一步的研究表明,DH 不影响 CD4 T 细胞的激活、分化和凋亡。相反,它能显著抑制常规 CD4 T 细胞的增殖。机制研究表明,DH 处理的 CD4 T 细胞由于 Cdc2(Tyr15)的抑制性磷酸化增强而部分停滞在细胞周期的 G2/M 期。此外,我们证明 DH 治疗可通过抑制自身反应性抗原特异性 CD4 T 细胞的增殖显著改善 EAU 。综上所述,本研究表明,DH 介导的 CD4 T 细胞增殖抑制可能为治疗 CD4 T 细胞介导的疾病提供一种有前途的治疗策略。