Renoprotection in crescentic glomerulonephritis by ANCA (C01)

我们将验证以下假设：受调节的细胞死亡途径，即坏死性上睑下垂和铁上睑下垂，介导自身免疫性anca相关血管增生（AV）的肾损伤，抑制这些途径的关键要素提供肾保护。具体来说，我们将描述(I) AV中中性粒细胞胞外陷阱（NETs）和单核细胞胞外陷阱（METs）产生的调节机制，（II）不同肾室中坏死和铁性细胞死亡，以及（III）导致AV诱导肾损伤的受调节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.