Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada.
Front Immunol. 2022 Apr 20;13:856694. doi: 10.3389/fimmu.2022.856694. eCollection 2022.
T helper (Th) cells play crucial roles in inflammation and adaptive immune system. Importantly, Th17 cells, a major pathogenic Th cell subset, are involved in the pathogenesis of multiple sclerosis (MS) and its classical animal modal experimental autoimmune encephalomyelitis (EAE). Previous studies have shown that parthenolide (PTL), a sesquiterpene lactone, possesses potent anti-cancer and anti-inflammatory activities. However, the immunosuppressive effect of PTL on the pathogenic Th17 cell and MS is unclear. In this study, we showed that PTL treatment could alleviate clinical symptoms by inhibiting inflammatory cell infiltration, reducing inflammation and demyelination of CNS. In addition, the mRNA expression of cytokines and inflammatory factors in CD4 T cells, especially Th1 and Th17 cells, reduced in both CNS and peripheral immune tissue of EAE mice. Furthermore, PTL could inhibit the reactivation of MOG-specific T cells and the differentiation of naïve CD4 T cells into Th17 cells . We also found that PTL inhibited nuclear factor kappa B (NF-κB) signaling and retinoid-related orphan receptor-γt (RORγt) in mouse Th17 cell and human Jurkat cell line. Taken together, our data demonstrated a critical immune-suppressive effect of PTL on autoimmune inflammation through regulating Th17 cells and the NF-κB/RORγt pathway.
辅助性 T 细胞（Th）在炎症和适应性免疫系统中发挥着关键作用。重要的是，Th17 细胞作为主要的致病性 Th 细胞亚群，参与了多发性硬化症（MS）及其经典动物模型实验性自身免疫性脑脊髓炎（EAE）的发病机制。先前的研究表明，小白菊内酯（PTL），一种倍半萜内酯，具有很强的抗癌和抗炎活性。然而，PTL 对致病性 Th17 细胞和 MS 的免疫抑制作用尚不清楚。在本研究中，我们发现 PTL 治疗可通过抑制炎症细胞浸润、减轻中枢神经系统的炎症和脱髓鞘来缓解临床症状。此外，EAE 小鼠中枢神经系统和外周免疫组织中 CD4 T 细胞（尤其是 Th1 和 Th17 细胞）的细胞因子和炎症因子的 mRNA 表达均降低。此外，PTL 可抑制 MOG 特异性 T 细胞的再活化和初始 CD4 T 细胞向 Th17 细胞的分化。我们还发现 PTL 可抑制核因子 kappa B（NF-κB）信号和鼠 Th17 细胞及人 Jurkat 细胞系中的视黄酸相关孤儿受体-γt（RORγt）。总之，我们的数据表明 PTL 通过调节 Th17 细胞和 NF-κB/RORγt 通路对自身免疫炎症具有重要的免疫抑制作用。
