Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: a role for neutrophil recruitment?
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.
Sayed
Blayne A
BA
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Christy
Alison L
AL
Walker
Margaret E
ME
Brown
Melissa A
MA
D019264:Adoptive Transfer; D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D002469:Cell Separation; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D008578:Meninges / Q000166:cytology / Q000276:immunology*; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D014409:Tumor Necrosis Factor-alpha