Role of Ga13-coupled receptor signaling during induction of intestinal Th17 cells.

T cells are major drivers of Inflammatory Bowel Disease (IBD) but the full set of factors promoting inflammatory intestinal T cell accumulation in affected individuals is not understood. We have found that deficiency in a signaling molecule (G-protein) in mouse hematopoietic cells leads to a reduction in inflammatory intestinal T cells. Here we will define the cell types requiring this signaling pathway for induction of inflammatory T cells in the intestine, and the upstream receptors involved. We will characterize how the pathway controls cell behavior to promote inflammatory T cell accumulation and determine the importance of the pathway in a mouse colitis model. These studies will provide a foundation for defining the contribution of the signaling pathway to human IBD and may lead to the identification of new avenues for therapeutic intervention to treat this condition.