Laboratory of Dermato-Immunology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, UConn Health, Farmington, CT, United States.
Front Immunol. 2021 Feb 25;12:628117. doi: 10.3389/fimmu.2021.628117. eCollection 2021.
Superoxide dismutase 3 (SOD3), a well-known antioxidant has been shown to possess immunomodulatory properties through inhibition of T cell differentiation. However, the underlying inhibitory mechanism of SOD3 on T cell differentiation is not well understood. In this study, we investigated the effect of SOD3 on anti-CD3/CD28- or phorbol myristate acetate (PMA) and ionomycin (ION)-mediated activation of mouse naive CD4 T cells. Our data showed that SOD3 suppressed the expression of activation-induced surface receptor proteins such as CD25, and CD69, and cytokines production. Similarly, SOD3 was found to reduce CD4T cells proliferation and suppress the activation of downstream pathways such as ERK, p38, and NF-κB. Moreover, naïve CD4T cells isolated from global SOD3 knock-out mice showed higher expression of CD25, CD69, and CD71, IL-2 production, proliferation, and downstream signals compared to wild-type CD4T cells. Whereas, the use of DETCA, a known inhibitor of SOD3 activity, found to nullify the inhibitory effect of SOD3 on CD4T cell activation of both SOD3 KO and wild-type mice. Furthermore, the expression of surface receptor proteins, IL-2 production, and downstream signals were also reduced in Th2 and Th17 differentiated cells upon SOD3 treatment. Overall, our data showed that SOD3 can attenuate CD4T cell activation through modulation of the downstream signalings and restrict CD4T cell differentiation. Therefore, SOD3 can be a promising therapeutic for T cell-mediated disorders.
超氧化物歧化酶 3（SOD3）是一种众所周知的抗氧化剂，通过抑制 T 细胞分化表现出免疫调节特性。然而，SOD3 对 T 细胞分化的抑制机制尚不清楚。在这项研究中，我们研究了 SOD3 对抗-CD3/CD28 或佛波醇肉豆蔻酸酯（PMA）和离子霉素（ION）介导的小鼠幼稚 CD4 T 细胞激活的影响。我们的数据表明，SOD3 抑制了激活诱导的表面受体蛋白如 CD25 和 CD69 的表达，以及细胞因子的产生。同样，SOD3 被发现减少了 CD4T 细胞的增殖，并抑制了下游途径如 ERK、p38 和 NF-κB 的激活。此外，从全球 SOD3 敲除小鼠中分离的幼稚 CD4T 细胞表现出更高的 CD25、CD69 和 CD71 的表达、IL-2 的产生、增殖和下游信号，与野生型 CD4T 细胞相比。然而，使用已知的 SOD3 活性抑制剂 DETCA 发现，它可以消除 SOD3 对 SOD3 KO 和野生型小鼠 CD4T 细胞激活的抑制作用。此外，在 SOD3 处理后，Th2 和 Th17 分化细胞中的表面受体蛋白表达、IL-2 产生和下游信号也减少。总的来说，我们的数据表明，SOD3 可以通过调节下游信号来减弱 CD4T 细胞的激活，并限制 CD4T 细胞的分化。因此，SOD3 可以成为治疗 T 细胞介导的疾病的有前途的方法。
