Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Life Sci. 2021 Jul 1;276:119395. doi: 10.1016/j.lfs.2021.119395. Epub 2021 Mar 27.
STAT3 signaling is critical for Th17 development that plays an important role in multiple sclerosis pathogenesis. To evaluate the anti-inflammatory and regulatory T cells effects of JAK1/2 and STAT3 inhibition, we assessed the JAK 1/2 inhibitor ruxolitinib effects on Th17 cell/Tregs balance.
Ruxolitinib was administered to experimental autoimmune encephalomyelitis (EAE) mice via oral gavage, and its effects were assessed. The expression of pro-inflammatory and anti-inflammatory cytokines, including IL-17A and IL-10, were analyzed by real-time PCR. The frequency of Th17 cells and Tregs were evaluated by flow cytometry.
Ruxolitinib ameliorated the EAE severity and decreased the proportion of Th17 cells and inflammatory markers levels. In contrast, the balance of Tregs and the level of anti-inflammatory cytokine were increased in ruxolitinib-treated mice. Furthermore, ruxolitinib markedly decreased the expression of Th17 related transcription factor, RORɣt, whereas FOXP3 expression associated with Treg differentiation was increased.
Our results show that ruxolitinib may be a promising therapeutic strategy for multiple sclerosis.
STAT3 信号通路对于 Th17 细胞的发育至关重要，而后者在多发性硬化症的发病机制中发挥着重要作用。为了评估 JAK1/2 和 STAT3 抑制的抗炎和调节性 T 细胞作用，我们评估了 JAK1/2 抑制剂鲁索利替尼对 Th17 细胞/Treg 平衡的影响。
通过口服灌胃给予实验性自身免疫性脑脊髓炎（EAE）小鼠鲁索利替尼，并评估其作用。通过实时 PCR 分析促炎和抗炎细胞因子（包括 IL-17A 和 IL-10）的表达。通过流式细胞术评估 Th17 细胞和 Treg 的频率。
鲁索利替尼改善了 EAE 的严重程度，并降低了 Th17 细胞的比例和炎症标志物水平。相比之下，在鲁索利替尼治疗的小鼠中，Treg 的平衡和抗炎细胞因子的水平增加。此外，鲁索利替尼显著降低了 Th17 相关转录因子 RORɣt 的表达，而与 Treg 分化相关的 FOXP3 表达增加。
我们的结果表明，鲁索利替尼可能是多发性硬化症的一种有前途的治疗策略。
