The Role of Dendritic Cells in Regulating the Gut-Brain Immune Axis in Ischemic Stroke

The long-term goal of this research program is to elucidate the role of intestinal microbiota in stroke pathobiology and develop the experimental framework for new preventative and therapeutic approaches for ischemic stroke. The project will test the hypothesis that the interaction of commensal intestinal microbiota with dendritic cells is a critical determinant of stroke outcome by modulating the immune system and inflammatory response to cerebral ischemia. Specifically, it will test the hypothesis that commensal intestinal microbiota modulate stroke outcome by acting on intestinal dendritic cells to either induce a tolerogenic or pro-inflammatory phenotype affecting T cell differentiation, with these intestinal immune changes propagating to the brain and meninges after stroke by increased immune cell trafficking. The research will determine (a) the roles of different dendritic cell populations in mediating the neuroprotective effects of altered microbiota and (b) the cellular and molecular targets of microbiota that lead to altered intestinal immunity and their importance for stroke outcome.