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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 100-110 |
| Number of pages | 11 |
| Journal | Journal of Autoimmunity |
| Volume | 73 |
| DOIs | |
| State | Published - Sep 1 2016 |
Funding
We thank Blayne Sayed for designing the mast cell-T cell co-culture system, Kelly Foy for assistance with mast cell quantification, Mark Ebel for assistance with RT-PCR analyses and Thirumala-Devi Kanneganti for the kind gift of the Il1b −/− mice. Grant support: NMSS RG 4684A5/1 (M.A.B), NIH F31 NS084691 (A.E.R.), NIH F31 NS068031 (M.W.-C.), Department of Immunology T32 ( 5 T32 AI 7047-33 ) and a grant from the Mayo Clinic Center for MS and Autoimmune Neurology (CMSAN) (M.W.-C.).
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
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
