Function of IL-22 and IL-9 in glomerulonephritis
The cytokines IL-22 and IL-9 are important regulators of tissue responses in inflammation and under homeostatic conditions. They are produced by T cell subsets and cells of the innate immune system. While IL-22 signaling exclusively targets tissue resident cells, IL-9 mainly exerts its effect by modulating the function of immune cells in an auto- and paracrine manner. Both cytokines have been implicated in autoimmune inflammation, as well as in tissue remodeling and repair processes. The role of these mediators in kidney disease is largely unknown. The proposed project will investigate IL-22- and IL-9-producing immune cells and their function in the immunopathogenesis of glomerulonephritis (GN). By using fluorescent reporter mice for IL-22 and IL-9, as well as cytokine-deficient mice and blocking antibodies, we will address the expression pattern and function of the two cytokines in mouse models of GN. In addition, we will characterize IL-22+ and IL-9+ cells in the blood and kidney of patients with GN and analyze changes in these cell populations under immunosuppressive therapy. The long-term aim of this project is to increase the understanding of IL-22 and IL-9 biology in renal inflammation and to potentially identify novel therapeutic targets for treatment of patients with immune-mediated glomerular disease.