We propose that mast cell regulation of immune responses in EAE (and by extension, MS) occurs through several mechanisms. These include: a) alteration of the blood-brain barrier to facilitate entry of autoreactive T cells; b) release of pro-inflammatory cytokines such as TNF-a; c) regulation of T cell trafficking via chemokine expression or modulation of homing receptors; d) release of regulatory cytokines such as IL-4 and IL-10 to modulate an ongoing response; e) and direct damage of the myelin sheath through release of proteases/cytokines that contribute to """"""""epitope spreading"""""""" by releasing new antigen epitopes for presentation to T cells. In this application, we will use an established model of relapsing-remitting multiple sclerosis to examine some of the potential mechanisms that underlie mast cell effects on a disease course.
| Sayed, Blayne A; Walker, Margaret E; Brown, Melissa A (2011) Cutting edge: mast cells regulate disease severity in a relapsing-remitting model of multiple sclerosis. J Immunol 186:3294-8 |
| Sayed, Blayne A; Christy, Alison L; Walker, Margaret E et al. (2010) Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: a role for neutrophil recruitment? J Immunol 184:6891-900 |
