The activation of toll-like receptor 3 (TLR3) has been reported to attenuate astrocytes injury in central nervous system, but its effect on enteric glial cells (EGCs) remains unknown. Here, we confirmed that the residence of EGCs was regulated by TLR3 agonist (polyinosinic-polycytidylic acid, PIC) or TLR3/dsRNA complex inhibitor in dextran sulfate sodium (DSS)-induced mice. In vitro, TLR3 signaling prevented apoptosis in EGCs and drove the secretion of EGCs-derived glial cell line-derived neurotrophic factor, 15-hydroxyeicosatetraenoic acid and S-nitrosoglutathione. PIC preconditioning enhanced the protective effects of EGCs against the dysfunction of intestinal epithelial barrier and the development of colitis in DSS-induced mice. Interestingly, PIC stimulation also promoted the effects of EGCs on converting macrophages to an M2-like phenotype and regulating the levels of inflammatory cytokines, including IL-1β, TNF-α and IL-10, in DSS-induced mice. These findings imply that TLR3 signaling in EGCs may provide a potential target for the prevention and treatment of colitis.

据报道，Toll 样受体 3 (TLR3) 的激活可减轻中枢神经系统星形胶质细胞的损伤，但其对肠胶质细胞 (EGC) 的影响仍不清楚。在这里，我们证实，在葡聚糖硫酸钠（DSS）诱导的小鼠中，EGCs的停留受到TLR3激动剂（聚肌胞苷酸，PIC）或TLR3/dsRNA复合物抑制剂的调节。在体外，TLR3信号传导阻止EGC细胞凋亡，并驱动EGC细胞衍生的神经胶质细胞系衍生的神经营养因子、15-羟基二十碳四烯酸和S-亚硝基谷胱甘肽的分泌。 PIC 预处理增强了 EGC 对 DSS 诱导小鼠肠上皮屏障功能障碍和结肠炎发展的保护作用。有趣的是，在 DSS 诱导的小鼠中，PIC 刺激还促进了 EGC 将巨噬细胞转化为 M2 样表型并调节炎性细胞因子（包括 IL-1β、TNF-α 和 IL-10）水平的作用。这些发现表明 EGC 中的 TLR3 信号传导可能为预防和治疗结肠炎提供潜在靶点。