Superoxide Dismutase 3 Controls the Activation and Differentiation of CD4T Cells.

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.