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

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

  • J Exp Med. 2019 Nov 4;216(11):2562-2581. doi: 10.1084/jem.20190377.
Sheng Li  # 1,  Yuqing Wu  # 1,  Dongxue Yang 1,  Chunyan Wu 1,  Chunmei Ma 1,  Xue Liu 1,  Paul N Moynagh 2 3,  Bingwei Wang 4,  Gang Hu 5,  Shuo Yang 6
Affiliations

Affiliations

  • 1 Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
  • 2 Maynooth University Human Health Research Institute, Department of Biology, National University of Ireland Maynooth, Maynooth, Ireland.
  • 3 Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.
  • 4 Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, China bingweiwang@njucm.edu.cn.
  • 5 Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, China ghu@njmu.edu.cn.
  • 6 Department of Immunology, Key Laboratory of Immunological Environment and Disease, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China shuoyang@njmu.edu.cn.
  • # Contributed equally.
PMID: 31467036 DOI: 10.1084/jem.20190377
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.

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