Immune regulatory mechanisms of renal inflammation

CD4+ T cells play a unique role in the pathogenesis of autoimmune disease, including human and experimental crescentic glomerulonephritis (GN). In particular TH1 and TH17 cells seem to mediate inflammatory renal tissue damage. In a mouse model of crescentic GN, we have shown recently that Foxp3+ regulatory T cells (Tregs) participate in regulation and suppression of the destructive immune response by production of IL-10 and down-modulation of IFNγ and IL-17. However, our results indicate that besides Foxp3+ Tregs and IL-10 other immune-regulatory molecules and cells might contribute to immune-regulation in the kidney. Therefore, we will address the following issues in this project:

1. Identification of cells expressing co-inhibitory molecules PD-1/PD-L1 or BTLA and analysis of their relative role for suppression of T cell responses during acute GN.

2. Assessment of the relative contribution of dendritic cell and CD4+ T cell derived IL-10 for protection from GN.

3. Analysis of different renal parenchymal cells for their function as non-professional antigen-presenting cells and their contribution to either immune-activation or immune-regulation in the kidney. In summary, our studies will result in a better understanding of the regulation of the local immune response in the kidney.

A02 Tiegs