Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: A role for neutrophil recruitment?

Blayne A. Sayed, Alison L. Christy, Margaret E. Walker, Melissa A. Brown

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Mast cells contribute to the pathogenesis of experimental autoimmune encephalomyelitis, a rodent model of the human demyelinating disease multiple sclerosis. Yet their site and mode of action is unknown. In both diseases, myelin-specific T cells are initially activated in peripheral lymphoid organs. However, for disease to occur, these cells must enter the immunologically privileged CNS through a breach in the relatively impermeable blood-brain barrier. In this study, we demonstrate that a dense population of resident mast cells in the meninges, structures surrounding the brain and spinal cord, regulate basal CNS barrier function, facilitating initial T cell CNS entry. Through the expression of TNF, mast cells recruit an early wave of neutrophils to the CNS.We propose that neutrophils in turn promote the blood-brain barrier breach and together with T cells lead to further inflammatory cell influx and myelin damage. These findings provide specific targets for intervention in multiple sclerosis as well as other immune-mediated CNS diseases.

Original languageEnglish (US)
Pages (from-to)6891-6900
Number of pages10
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - Jun 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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