Renoprotection in crescentic glomerulonephritis by ANCA (C01)

我们将检验一种假设，即调节的细胞死亡途径，即坏死性下垂和铁性下垂，在自身免疫性ANCA相关血管炎(AV)中介导肾脏损伤，并且抑制这些途径的关键元件提供肾脏保护。具体地说，我们将描述(I)调控AV中性粒细胞胞外陷阱(Net)和单核细胞胞外陷阱(Mets)产生的机制，(Ii)不同肾间隔中坏死性和铁性细胞死亡的机制，以及(Iii)导致AV引起肾脏损伤的调控细胞死亡途径的治疗靶点。我们的研究将阐明AV疾病的机制，并确定肾脏保护治疗策略，然后将在临床试验中进行测试。

We will test the hypothesis that regulated cell death pathways, namely necroptosis and ferroptosis, mediate kidney injury in autoimmune ANCA-associated vasculitides (AV) and that inhibiting key elements of these pathways provides renoprotection. Specifically, we will characterize (I) mechanisms involved in the regulation of the generation of neutrophil extracellular traps (NETs) and monocyte extracellular traps (METs) in AV, (II) necroptotic and ferroptotic cell deaths in the different kidney compartments, and (III) therapeutic targets of regulated cell death pathways that cause AV-induced kidney damage. Our studies will elucidate AV disease mechanisms and identify renoprotective treatment strategies that will then be tested in clinical trials.