Abstract：
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.
摘要：
在这项研究中,我们检查了使用各种刺激的儿童MOGAD患者（n=4，未经治疗的缓解样本）和健康对照（n=5）的CD4T细胞活化，了解抗原特异性和旁观者机制如何促进MOGAD中CD4T细胞活化。TNFα,发现IL6和MOG肽池通过使用免疫标记测量调节因子（A20，IκBα）和磷酸化亚基（磷酸-p65和磷酸-STAT3）的表达来激活NF-κB或STAT3途径。泼尼松龙逆转NF-κB和STAT3的激活，并增加A20和IκBα的表达。在某些CD4T细胞亚群中，TNFR阻断部分逆转NF-κB活化，但不影响STAT3激活。我们观察到响应于各种刺激的NF-κB和STAT3的激活在MOGAD（缓解）和HC中表现基本相同。IL6刺激导致MOGAD患者在75分钟时更高的STAT3磷酸化，特别是在中枢和效应记忆CD4T细胞中（具有未调整的p值）。这些发现提示MOGAD中NF-κB和STAT3途径的潜在治疗靶向。需要进一步的研究来验证延长STAT3磷酸化的重要性及其与IL6受体阻滞剂治疗反应的相关性。
