Function of chemokine receptors in T cell-mediated glomerulonephritis

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The infiltration of CD4+ T cells into the kidney is a typical finding in human and experimental crescentic glomerulonephritis. We and others have shown that Th1 and Th17 cell-mediated immune responses, in particular, contribute to renal tissue injury, while Tregs could have beneficial properties. The underlying mechanisms of renal T cell subset trafficking and activation are incompletely understood. However, chemokines and chemokine receptors are thought to play a crucial role. In the next funding period, we wish to address the following points: 1. Characterization of the chemokine receptor expression profile of CD4+ T cell subsets and definition of their functional role for T cell trafficking and consecutive kidney damage in a murine model of crescentic glomerulonephritis, with specific focus on the leukocyte subset-specific function of CXCR3. 2. Clarification of the interaction between the renal Th17/IL-17 immune response and the chemokine system. 3. Establishment of fluorescence-based in vivo microscopy techniques for the visualization of renal T cell migration and interaction under homeostatic and inflammatory conditions. 4. Analysis of the expression pattern of target molecules in blood samples and renal biopsies of patients with glomerulonephritis. In summary our studies will result in a better understanding of chemokine/chemokine receptor-regulated T cell trafficking and its role in renal tissue injury. This might facilitate target-specific therapy in human T cell-mediated glomerulonephritis.