Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose symptoms include communication deficits, a lack of social skills, and stereotyped repetitive behaviors. We used BTBR T⁺ Itpr3^tf/J (BTBR) mice, a model that demonstrates most of the core behavioral features of ASD, such as decreased sociability and high levels of repetitive behaviors. Currently, there is no treatment available that is able to improve most of the ASD disorder symptoms; thus, finding novel therapies is immediately required. Stat3 inhibitors are potential targets in the treatment of several immune disorders. The aim of the present study was to investigate the effects of S3I-201, a selective Stat3 inhibitor, to determine its potential mechanism in BTBR mice. In this study, we first examined the effects of S3I-201 on repetitive behavior and marble burying. We also examined the treatment of S3I-201 on Th1 (IFN-γ and T-bet), Th17 (IL-17A, RORγt, Stat3, IL-21, and IL-22), and T regulatory (Treg, Foxp3 and Helios) production in spleen CD4⁺ T cells. We further assessed Th1, Th17, and Treg mRNA and protein expression levels in brain tissues. S3I-201 treatment in BTBR mice significantly prevents marble burying and repetitive behavior. Furthermore, S3I-201 administration causes a considerable decrease in IFN-γ, T-bet, IL-17A, RORγt, Stat3, IL-21, and IL-22 levels, and increases in Foxp3 and Helios production CD4⁺ T cells in BTBR mice. Additionally, S3I-201 treatment also significantly decreases Th1 and Th17 levels, and increases Treg mRNA and protein expression levels. Therefore, these results suggest that S3I-201 could be considered as a therapeutic option for ASD.

自闭症谱系障碍（ASD）是一种神经发育障碍，其症状包括沟通不足，缺乏社交技巧和刻板的重复行为。我们使用了BTBR T ⁺ Itpr3 ^tf/ J（BTBR）小鼠，该模型演示了ASD的大多数核心行为特征，例如社交能力下降和重复行为的高水平。目前，尚无能够改善大多数ASD障碍症状的治疗方法。因此，立即需要寻找新的疗法。Stat3抑制剂是治疗几种免疫疾病的潜在靶标。本研究的目的是研究选择性Stat3抑制剂S3I-201的作用，以确定其在BTBR小鼠中的潜在机制。在这项研究中，我们首先检查了S3I-201对重复行为和大理石掩埋的影响。我们还检查了Th1（IFN-γ和T-bet），Th17（IL-17A，RORγt，Stat3，IL-21和IL-22）和T调节剂（Treg，Foxp3和Helios）对S3I-201的治疗）脾CD4 ^+的生产T细胞。我们进一步评估了脑组织中的Th1，Th17和Treg mRNA和蛋白质表达水平。在BTBR小鼠中进行S3I-201处理可显着防止大理石掩埋和重复行为。此外，S3I-201给药会导致BTBR中的IFN-γ，T-bet，IL-17A，RORγt，Stat3，IL-21和IL-22水平显着降低，并增加Foxp3和Helios产生CD4 ⁺ T细胞老鼠。另外，S3I-201处理还显着降低Th1和Th17水平，并增加Treg mRNA和蛋白质表达水平。因此，这些结果表明，S3I-201可被视为ASD的治疗选择。