Grant: CIHR Fellowship

The gut is home to a subtype of immune cells called T helper 17 cells, or "Th17" cells. These cells are known to maintain balance in the gut; they strengthen the gut's barrier to prevent the resident commensal bacteria from leaving and causing damage in other organs. However, these same Th17 cells that play a protective role in the gut can be stressed into leaving the gut, entering the central immune system, and causing inflammation. This inflammation causes symptoms in mice that mirror those experienced by people with multiple sclerosis. There is evidence from mouse models and humans that show an immune signaling protein called IL-23 may be the stressor that provokes Th17 cells to transition from gut protector to nervous system attacker. However, it remains unclear what cell types release IL-23 in the gut and how IL-23 signals in Th17 cells to change their function. My work will use cutting-edge single-cell technologies and engineered mouse models of multiple sclerosis to look at how IL-23, and the cells that make it, impact Th17 cell gene expression and protein function. These fine, detailed analyses will identify specific genes and proteins that play key roles in transitioning Th17 cells into a pathogenic state. I will then perform experiments to validate which genes and proteins can be targeted therapeutically to prevent and/or reverse multiple sclerosis symptoms in mice. These experiments will identify signaling pathways that may be shared with humans, and therefore provide new therapeutic targets for the treatment of multiple sclerosis.