Grant: CIHR Fellowship

Multiple Sclerosis (MS) is a devastating autoimmune disorder of the central nervous system (CNS) caused by the progressive deterioration of myelin, a substance that coats nerve cells. The development and progression of MS results from pathogenic immune effector T cells that harbor specificity for myelin antigens. A key mediator that potentiates pathogenic responses in MS is the cytokine, IL-23, which skews myelin-specific T cells towards an inflammatory phenotype. Recently however, we have found that a subunit of IL-23, p40, forms a novel complex with a soluble protein, CD5L, and acts to suppress the activity of pathogenic T cells and inhibits the development of MS in mice. Therefore, the opposing functions of IL-23 signaling on auto-reactive T cells in MS is poorly understood. My research will focus on delineating the exact process by which the p40:CD5L complex acts on auto-reactive T cells to suppress inflammation while clarifying its opposing contribution in IL-23-mediated pathogenic responses. I will use a combination of cutting-edge techniques including genetic engineering, single-cell transcriptomics, and high dimensional immune profiling to address these goals. This investigation will deepen our understanding of the mechanism that drives MS pathology and provide important insight into the development of new therapeutics that can selectively inhibit pathogenic auto-reactive T cells.