Regulation of the Th17 response in glomerulonephritis

肾小球肾炎中 Th17 反应的调节

• 批准号: 226130106
• 负责人: Professor Dr. Oliver Michael Steinmetz
• 金额: --
• 依托单位: III. Medizinische Klinik und Poliklinik (Nephrologie, Rheumatologie - Nierentransplantation - Sektion Endokrinologie/Diabetologie)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/226130106?language=en
• 关键词: Regulation; Th17; response; glomerulonephritis

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.

最近的研究，包括我们自己的研究，已经证明了CD4+ T辅助细胞（Th）在增殖性肾小球肾炎（GN）发病机制中的核心作用。特别是Th1型的辅助性T细胞反应被认为是致病性的中心。然而，新发现的Th17反应被证明对肾损伤的发展具有类似的重要性。因此，靶向Th17反应似乎是开发肾小球肾炎新疗法的有益策略。然而，Th17反应的许多方面在很大程度上仍不清楚。这包括Th17细胞的分化，它们的可塑性以及它们通过抗炎机制的反调节。最近的研究引入了Th17谱系特异性调节性T细胞（Treg17）的概念，它与促炎的Th17细胞有许多发育上的相似之处。迄今为止，这些抗炎的Th17谱系特异性Tregs的功能重要性仍然很大程度上未知。目前的申请旨在表征三个中心分子诱导Th17反应，IL-6和关键转录因子STAT3和RORγt在GN中的作用。此外，我们将研究STAT3和RORγt在Treg17生成和Th17细胞可塑性中的可能作用。我们的目标是更好地理解Th17在GN中的反应，特别关注诱导和反调控。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选择。