Mast cell inflammasome activity in the meninges regulates EAE disease severity

Abigail E. Russi, Margaret E. Walker-Caulfield, Melissa A. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Inflammasomes are multiprotein complexes that assemble in response to microbial and other danger signals and regulate the secretion of biologically active IL-1β and IL-18. Although they are important in protective immunity against bacterial, viral and parasitic infections, aberrant inflammasome activity promotes chronic inflammation associated with autoimmune disease. Inflammasomes have been described in many immune cells, but the majority of studies have focused on their activity in macrophages. Here we discuss an important role for mast cell-inflammasome activity in EAE, the rodent model of multiple sclerosis, a CNS demyelinating disease. We review our evidence that mast cells in the meninges, tissues that surround the brain and spinal cord, interact with infiltrating myelin-specific T cells in early disease. This interaction elicits IL-1β expression by mast cells, which in turn, promotes GM-CSF expression by T cells. In view of the essential role that GM-CSF plays in T cell encephalitogenicity, we propose this mast cell-T cell crosstalk in the meninges is critical for EAE disease development.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
JournalClinical Immunology
Volume189
DOIs
StatePublished - Apr 2018

Keywords

  • CNS demyelinating disease
  • EAE
  • GM-CSF
  • IL-1β
  • Inflammasome
  • Mast cells
  • Meninges
  • Multiple sclerosis
  • T cell pathogenicity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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