title: Meningeal mast cell-T cell crosstalk regulates T cell encephalitogenicity.
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.
authors.affiliation: Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
authors.forename: Abigail E
authors.initials: AE
authors.lastname: Russi
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Walker-Caulfield
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.affiliation: Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. Electronic address: m-brown12@northwestern.edu.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000368:Aged; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D008578:Meninges / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020170:Caspase 1
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