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Updated: Jan 20, 2026
Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis
Published on: September 9, 2022
Gasdermin D in peripheral myeloid cells drives neuroinflammation in experimental autoimmune encephalomyelitis
Sheng Li1, Yuqing Wu1, Dongxue Yang1
1Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
Abstract:
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.
Insights
Gasdermin D (GSDMD) drives neuroinflammation in experimental autoimmune encephalomyelitis (EAE). GSDMD deficiency in myeloid cells impairs immune cell infiltration, reducing EAE pathogenesis and demyelination.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- The NLRP3 inflammasome is crucial for experimental autoimmune encephalomyelitis (EAE) pathogenesis.
- Gasdermin D (GSDMD) is a key pyroptosis executioner downstream of NLRP3, but its role in EAE is unclear.
Purpose of the Study:
- To investigate the role of gasdermin D (GSDMD) in the pathogenesis of EAE.
- To elucidate the function of GSDMD in myeloid cells during EAE.
Main Methods:
- Analysis of GSDMD protein levels in the central nervous system (CNS) of EAE mice.
- Utilizing GSDMD knockout (KO) mice, particularly those deficient in peripheral myeloid cells.
- Assessing immune cell infiltration, neuroinflammation, demyelination, and T cell activation/differentiation in EAE models.
- Investigating the effect of inflammasome-related cytokines on EAE pathogenesis in GSDMD KO mice.
Main Results:
- GSDMD protein levels were significantly elevated in the CNS of EAE mice, particularly around blood vessels.
- GSDMD deficiency in peripheral myeloid cells suppressed EAE pathogenesis by impairing immune cell infiltration into the CNS.
- Loss of GSDMD reduced neuroinflammation and demyelination.
- GSDMD deficiency hindered T cell activation, differentiation, and CNS infiltration in EAE.
- Partial rescue of EAE pathogenesis was observed in GSDMD KO mice upon administration of inflammasome-related cytokines.
Conclusions:
- Gasdermin D (GSDMD) plays a critical role in driving neuroinflammation and demyelination in EAE.
- GSDMD in peripheral myeloid cells is essential for immune cell trafficking to the CNS during EAE.
- Targeting GSDMD may offer a therapeutic strategy for neuroinflammatory diseases like EAE.
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