Journal
JOURNAL OF AUTOIMMUNITY
Volume 73, Issue -, Pages 100-110Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2016.06.015
Keywords
Experimental autoimmune encephalomyelitis (EAE); Multiple sclerosis (MS); Meninges; Mast cells; GM-CSF; IL-1 beta; Inflammasome; Caspase-1; T helper cells; T cell licensing; Myeloid cells
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Funding
- NMSS [RG 4684A5/1]
- NIH [F31 NS084691, F31 NS068031]
- Department of Immunology T32 [5 T32 AI 7047-33]
- Mayo Clinic Center for MS and Autoimmune Neurology (CMSAN)
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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-l-dependent IL-1 beta 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. (C) 2016 Elsevier Ltd. All rights reserved:
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