Mast cell inflammasome activity in the meninges regulates EAE disease severity

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

Research output: Contribution to journalArticle

  • 9 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.

LanguageEnglish (US)
JournalClinical Immunology
DOIs
StateAccepted/In press - Dec 17 2015

Fingerprint

Inflammasomes
Meninges
Mast Cells
T-Lymphocytes
Granulocyte-Macrophage Colony-Stimulating Factor
Multiprotein Complexes
Parasitic Diseases
Interleukin-18
Central Nervous System Diseases
Demyelinating Diseases
Virus Diseases
Myelin Sheath
Bacterial Infections
Autoimmune Diseases
Multiple Sclerosis
Immunity
Rodentia
Spinal Cord
Macrophages
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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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.",
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Mast cell inflammasome activity in the meninges regulates EAE disease severity. / Russi, Abigail E.; Walker-Caulfield, Margaret E.; Brown, Melissa A.

In: Clinical Immunology, 17.12.2015.

Research output: Contribution to journalArticle

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