Pathogenic Th17 cells play a key role in the pathogenesis of many autoimmune diseases. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is the commonly used animal model for human MS and is characterized by autoreactive CD4⁺T cells attacking autoantigens in the CNS and causing myelin sheath damage. Although the recombinant BTN2A2-IgG2aFc (BTN2A2-Ig) fusion protein has been shown to inhibit T cell functions in vitro, it's unclear whether BTN2A2-Ig affects pathogenic Th17 cells and EAE development. We show here that BTN2A2-Ig protein attenuates established EAE, as compared with control Ig protein treatment. This is associated with reduced activation and proliferation of T cells in BTN2A2-Ig-treated EAE mice. Furthermore, BTN2A2-Ig protein inhibits the differentiation of CD4 naïve T cells into pathogenic Th17 cells and reduces the expression levels of Th1/Th17 cytokines and the Th1/Th17 pathway related genes and proteins but increases the expression levels of Th2-related genes and proteins. Our studies not only provide new insights into the mechanisms by which BTN2A2-Ig affects T cells, but also have the potential to provide a new strategy to treat MS and other autoimmune diseases.

致病性 Th17 细胞在许多自身免疫性疾病的发病机制中发挥着关键作用。多发性硬化症（MS）是一种中枢神经系统（CNS）的自身免疫性疾病。实验性自身免疫性脑脊髓炎（EAE）是人类多发性硬化症常用的动物模型，其特征是自身反应性CD4 ⁺ T细胞攻击中枢神经系统中的自身抗原并引起髓鞘损伤。尽管重组 BTN2A2-IgG2aFc (BTN2A2-Ig) 融合蛋白已被证明可以在体外抑制 T 细胞功能，但尚不清楚 BTN2A2-Ig 是否影响致病性 Th17 细胞和 EAE 的发展。我们在此表明​​，与对照 Ig 蛋白治疗相比，BTN2A2-Ig 蛋白可减轻已确定的 EAE。这与 BTN2A2-Ig 治疗的 EAE 小鼠中 T 细胞的活化和增殖减少有关。此外，BTN2A2-Ig蛋白抑制CD4幼稚T细胞分化为致病性Th17细胞，降低Th1/Th17细胞因子以及Th1/Th17途径相关基因和蛋白的表达水平，但增加Th2相关基因和蛋白的表达水平。我们的研究不仅为 BTN2A2-Ig 影响 T 细胞的机制提供了新的见解，而且有可能提供治疗 MS 和其他自身免疫性疾病的新策略。