This project is dedicated to examining the role of mast cells in relapsing remitting experimental autoimmune encephalomyelitis (EAE), a widely studied murine model of human relapsing-remitting multiple sclerosis (MS). In both MS and EAE, encephalitogenic CD4+ T cells specific for myelin antigens mediate the pathogenic autoimmune response. In order to address the role of mast cells in relapsing remitting EAE, a novel strain of mast cell deficient mice will be utilized for both in vitro and in vivo experiments. This project will include the assessment of the effect of a mast cell deficiency on relapsing remitting EAE disease in general and an extensive examination of T cell function in these novel mast cell deficient mice. Furthermore, elucidating the disease relevant mast cell populations and their contribution to epitope spreading, a well- characterized molecular mechanism implicated in disease progression in relapsing remitting EAE, will be a primary focus. Although MS is the most common inflammatory disease of the CNS, there is currently no cure for MS. This project's focus is identify the role of mast cells in this clinically relevant murine model of human MS in order to identify mast cell specific functions as potential therapeutic targets. Relevance: MS affects more than 2.5 million people worldwide. Although, there are multiple therapies available, these therapies carry with them side effects ranging from flu-like symptoms to lethal infections of the central nervous system. There is currently no cure for MS. One of the multiple forms of MS subjects patients to difficulties with visual disturbances, bowel and bladder incontinence, sensory and motor disturbances, and lack of coordination within periods of disease manifestation and times of disease recovery. This form of MS is known as relapsing remitting MS which affects ~85% of all MS patients. The model of EAE that will be used in this proposed research manifests as relapsing remitting disease. This research specifically focuses on this most clinically relevant disease model for human MS in order to identify novel therapeutic targets.
|Russi, Abigail E; Walker-Caulfield, Margaret E; Guo, Yong et al. (2016) Meningeal mast cell-T cell crosstalk regulates T cell encephalitogenicity. J Autoimmun 73:100-10|
|Walker-Caulfield, Margaret E; Hatfield, Julianne K; Brown, Melissa A (2015) Dynamic changes in meningeal inflammation correspond to clinical exacerbations in a murine model of relapsing-remitting multiple sclerosis. J Neuroimmunol 278:112-22|
|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|