Dysregulation of immune cell function in autoimmunity
MS is a complex disease with no known cause or cure. Based on genetic and pathology data, we know that the immune system plays a very important role in this disease. My lab is interested in how immune cells become activated with the CNS environment. In particular, using an animal model of MS (Experimental Autoimmune Encephalomyelitis), we have been studying immune cell rich structures found in the meninges. In addition, Immunologists have learned that B-lymphocytes play a very important role in modulating autoimmunity. In collaboration with a multi-disciplinary team of neuroimmunologists and using a number of animal and human model systems, we are currently exploring how pro- and anti- inflammatory B cells impact MS pathogenesis. Lastly, we are particularly interested in how the mucosal immune system in the gut influences autoimmune responses in the CNS. This work is supported by the MS Society of Canada (single PI grant) and the MS Society Research Foundation of Canada (team grant with Drs. Amit Bar-Or and Alexandre Prat).
Why are autoimmune disease on the rise in Canada?
The highest prevalence of chronic inflammatory diseases is found in northern latitude countries where a 3- 5-fold incidence increase has been observed over the last 30-50 years. Such a rapid rise in disease can only be explained by environmental changes, the nature of which remains unknown. We have focused on the gut microbiome as a possible modifier of disease risk in genetically susceptible individuals. The gut microbiome is one of the most densely populated bacterial communities, and, in the gut, interactions between the microbiome and the host immune system are played out across a thin barrier comprised of epithelial cells. Using a combination of animal models and human tissues, we are examining interactions between the microbiome and the mucosal immune system, in particular mucosal B lineage cells such as IgA+ plasma cells. We are exploring how this large reservoir of IgA+ plasma cells reflects ongoing responses to the microbiome and what role IgA+ plasma cells may play in inflammatory responses. This work is supported by Canadian Institutes of Health Research Research (single PI grant) and the Connaught Foundation (team grant, JG as principal PI).
TNF family members and immune cell biology
TNF family members play diverse roles in the immune system, and therapies for treatment of some autoimmune disease are targeted at TNF family members. We have a long-standing interest in both the Lymphtooxin and BAFF pathways in the context of chronic inflammatory conditions. Using a combination of animal models and human systems, we are interrogating the role of these pathways in a variety of immune contexts including mucosal IgA responses, germinal centre reactions and Dendritic Cell biology. This work is supported by Canadian Institutes of Health Research Research (single PI grant) and the Kidney Foundation (single PI grant).