Aug 31, 2019

Gasdermin D in peripheral myeloid cells drives neuroinflammation in experimental autoimmune encephalomyelitis

The Journal of Experimental Medicine
Sheng LiShuo Yang


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.

  • References37
  • Citations1


  • References37
  • Citations1


Mentioned in this Paper

Immune Effector Cell
Blood Vessel
Experimental Autoimmune Encephalomyelitis
Myeloid Cells
Administration Procedure
Vitamin D Deficiency
Cell Differentiation Process

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