P10 Prof. Dr. Kurts/Prof. Dr. Hoppe
Dendritic cells, inflammasome activation and regulatory T cells in kidney fibrosis

Renal dendritic cells producing inflammasomes promote inflammatory kidney disease, whereas regulatory T cells attenuate this process. Within this project we aim to block kidney fibrosis progression by modulation of these cells and/or the inflammasome. Chronic tubulointerstitial inflammation frequently leads to renal fibrosis and terminal kidney failure. Based on the important roles of dendritic cells (DC) in inflammation and immunology, we are studying their involvement in renal fibrosis in this project. We discovered that DCs colonize the kidney in a CX3CR1-dependent manner and aggravate an experimental glomerulonephritis model, by augmenting nephritogenic T cell responses. Our current aim is to employ a variety of genetic tools to better understand how kidney DCs regulate renal inflammation and fibrosis. We will study the role of the inflammasome, an important fibrosis promoter in other organs, which is produced by renal DCs. We wish to clarify the role of inflammasome components like NLRP3 and ASC and identify the cell(s) in which inflammasome activation takes place. Furthermore, we wish to understand the role of regulatory T cells (Tregs), which others and we recently showed to suppress experimental glomerulonephritis. Our work is aimed at a better understanding of intrarenal anti-inflammatory processes relevant during renal fibrogenesis, which may be exploited for therapeutic purposes.

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