CD4+ T cells orchestrate the immune response and play a unique role in autoimmune and chronic inflammatory diseases. The characterization of TH17 cells, a distinct IL-17 cytokine producing CD4+ T cell subset, has significantly advanced our current understanding of the pathogenic mechanisms of organ-specific immunity. Our group and others have shown that the recruitment of TH17 cells to the inflamed kidney drives renal tissue damage in experimental and possibly human crescentic glomerulonephritis (GN). Despite these advances, the biological functions and signalling pathways of the TH17/IL-17 axis leading to organ injury remain to be fully understood. To achieve this, we have the following aims: 1) Investigation of the mechanisms and function of renal CD4+ T cell trafficking, in particular the molecular events controlling their emigration from (or retention in) the kidney. To this end, we will use mice engineered to express the photoconvertible fluorescent protein, Kaede; 2) Analyses of the TH17/IL-17 cytokine family function, their receptors and their associated chemokines in immune-mediated renal diseases; and 3) High-dimensional analysis of the CD4+ T cell immune response of crescentic GN patients using a systems immunology approach. In summary, continuing this project will result in a better understanding of CD4+ T cell trafficking and of TH17/IL-17 cytokine network involvement in renal autoimmune diseases. These studies are essential to develop pathogenesis-based and personalized treatments to target the TH17/IL-17 pathway.