NF-κB and STAT3 activation in CD4 T cells in pediatric MOG antibody-associated disease

In this study, we examined CD4 T cell activation using various stimuli in pediatric MOGAD patients (n = 4, untreated remission samples) and healthy controls (n = 5), to understand how both antigen-specific and bystander mechanisms contribute to CD4 T cell activation in MOGAD. TNFα, IL6, and MOG peptide pool were found to activate NF-κB or STAT3 pathways by measuring the expression of regulators (A20, IκBα) and phosphorylated subunits (phospho-p65 and phospho-STAT3) using immunolabeling. Prednisolone reversed activation of both NF-κB and STAT3 and increased the expression of A20 and IκBα. TNFR blocking partially reversed NF-κB activation in certain CD4 T cell subsets, but did not effect STAT3 activation. We observed that activation of NF-κB and STAT3 in response to various stimuli behaves mostly same in MOGAD (remission) and HC. IL6 stimulation resulted in higher STAT3 phosphorylation in MOGAD patients at 75 min, specifically in central and effector memory CD4 T cells (with unadjusted p-values). These findings suggest the potential therapeutic targeting of NF-κB and STAT3 pathways in MOGAD. Further investigation is needed to validate the significance of extended STAT3 phosphorylation and its correlation with IL6 receptor blocker treatment response. [Display omitted] •Peak response to TNFα, IL6, PMA/Ionomycin were similar in MOGAD and controls.•IL6 caused higher STAT3 phosphorylation in MOGAD Tcm and Tem at 75 min.•Prednisolone inhibited NFκB and STAT3 activation induced by MOG peptides and CD3/CD28•TNFR blockade partially reduced NFκB activation in specific CD4 subsets but not STAT3 activation•IL6 stimulation decreased A20 (Tcm,Tem, Tnaive) and IκBα(Tcm, Tnaive) levels