The NLRP3 inflammasome is critical for EAE pathogenesis; however, the role of gasdermin D (GSDMD), a newly identified pyroptosis executioner downstream of NLRP3 inflammasome, in EAE has not been well defined. Here, we observed that the levels of GSDMD protein were greatly enhanced in the CNS of EAE mice, especially near the areas surrounding blood vessels. GSDMD was required for the pathogenesis of EAE, and GSDMD deficiency in peripheral myeloid cells impaired the infiltration of immune cells into the CNS, leading to the suppression of neuroinflammation and demyelination. Furthermore, the loss of GSDMD reduced the activation and differentiation of T cell in the secondary lymphoid organs and prevented T cell infiltration into CNS of EAE. The administration of inflammasome-related cytokines partially rescued the impairment of pathogenesis of EAE in GSDMD KO mice. Collectively, these findings provide the first demonstration of GSDMD in peripheral myeloid cells driving neuroinflammation during EAE pathogenesis.

NLRP3炎性小体对于EAE发病机制至关重要。然而，在EAE中，新近鉴定出的NLRP3炎性小体下游的发烧执行者gasdermin D（GSDMD）的作用尚未明确。在这里，我们观察到EAE小鼠中枢神经系统中GSDMD蛋白的水平大大提高，尤其是在血管周围区域附近。GSDMD是EAE的发病机制所必需的，外周髓样细胞中GSDMD的缺乏会削弱免疫细胞向CNS的浸润，从而抑制神经炎症和脱髓鞘。此外，GSMDD的丧失降低了次级淋巴器官中T细胞的活化和分化，并阻止了T细胞浸入EAE的CNS中。炎性体相关细胞因子的施用部分挽救了GSDMD KO小鼠中EAE的发病机理的损害。总的来说，这些发现首次证明了GSDMD在EAE发病过程中驱动神经炎症的外周髓样细胞中的表达。