Regulation of the Th17 response in glomerulonephritis

最近的研究，包括我们自己的，已经证明了中心作用的CD 4 + T辅助细胞（Th）在增生性肾小球肾炎（GN）的发病机制。特别是辅助性T细胞反应的Th 1型被认为是在致病性的中心。然而，新鉴定的Th 17应答显示对于肾损伤的发展具有类似的重要性。因此，靶向Th 17应答似乎是开发针对肾小球肾炎的新型治疗的有益策略。然而，Th 17反应的许多方面仍然很不清楚。这些包括Th 17细胞分化、它们的可塑性以及它们通过抗炎机制的反调节。最近的研究已经引入了Th 17谱系特异性调节性T细胞（Treg 17）的概念，其与其促炎Th 17对应物具有许多发育相似性。这些抗炎性Th 17谱系特异性Tclase的功能重要性迄今为止在很大程度上仍然未知。本申请旨在表征用于诱导Th 17应答的三种中心分子IL-6和关键转录因子STAT 3和RORγt在GN中的作用。此外，我们将研究STAT 3和RORγt对Treg 17生成和Th 17细胞可塑性的可能作用。我们的目标是更好地了解GN中的Th 17反应，特别关注诱导和反调节。这些新的见解可能有助于开发新的和更具体的治疗肾小球肾炎的治疗选择。

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.