Regulation of the Th17 response in glomerulonephritis

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Recent studies, including our own, have proven a central role of CD4+ T helper cells (Th) in the pathogenesis of proliferative glomerulonephritis (GN). Particularly the T helper cell response of the Th1 type was considered to be in the centre of pathogenicity. However, the newly identified Th17 response was shown to be of similar importance for development of kidney injury. Targeting the Th17 response therefore appears to be a rewarding strategy for the development of novel treatments against glomerulonephritis. Many aspects of the Th17 response, however, remain largely unclear. These include Th17 cell differentiation, their plasticity and also their counter-regulation by anti-inflammatory mechanisms. Very recent studies have introduced the concept of Th17 lineage specific regulatory T cells (Treg17) which share many developmental similarities with their pro-inflammatory Th17 counterparts. The functional importance of these anti inflammatory, Th17 lineage specific Tregs remains largely unknown to date. The current application aims to characterize the role of three central molecules for induction of the Th17 response, IL-6 and the key transcription factors STAT3 and RORγt in GN. Furthermore we will investigate possible roles of STAT3 and RORγt for Treg17 generation and Th17 cell plasticity. Our goal is to achieve a better understanding of the Th17 response in GN with a special focus on induction and counter regulation. These new insights might help to develop new and more specific therapeutic options for the treatment of glomerulonephritis.