Meningeal mast cell-T cell crosstalk regulates T cell encephalitogenicity

Abigail E. Russi, Margaret E. Walker-Caulfield, Yong Guo, Claudia F. Lucchinetti, Melissa A. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

GM-CSF is a cytokine produced by T helper (Th) cells that plays an essential role in orchestrating neuroinflammation in experimental autoimmune encephalomyelitis, a rodent model of multiple sclerosis. Yet where and how Th cells acquire GM-CSF expression is unknown. In this study we identify mast cells in the meninges, tripartite tissues surrounding the brain and spinal cord, as important contributors to antigen-specific Th cell accumulation and GM-CSF expression. In the absence of mast cells, Th cells do not accumulate in the meninges nor produce GM-CSF. Mast cell-T cell co-culture experiments and selective mast cell reconstitution of the meninges of mast cell-deficient mice reveal that resident meningeal mast cells are an early source of caspase-1-dependent IL-1β that licenses Th cells to produce GM-CSF and become encephalitogenic. We also provide evidence of mast cell-T cell co-localization in the meninges and CNS of recently diagnosed acute MS patients indicating similar interactions may occur in human demyelinating disease.

Original languageEnglish (US)
Pages (from-to)100-110
Number of pages11
JournalJournal of Autoimmunity
Volume73
DOIs
StatePublished - Sep 1 2016

Keywords

  • Caspase-1
  • Experimental autoimmune encephalomyelitis (EAE)
  • GM-CSF
  • IL-1beta
  • Inflammasome
  • Mast cells
  • Meninges
  • Multiple sclerosis (MS)
  • Myeloid cells
  • T cell licensing
  • T helper cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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