RGC-32 在免疫介导的肾脏疾病中介导促炎症和坏死通路。

IF 4.5 3区 医学 Q2 IMMUNOLOGY Clinical immunology Pub Date : 2024-06-13 DOI:10.1016/j.clim.2024.110279
Alexandru Tatomir , Sonia Vlaicu , Vinh Nguyen , Irina G. Luzina , Sergei P. Atamas , Cinthia Drachenberg , John Papadimitriou , Tudor C. Badea , Horea G. Rus , Violeta Rus
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引用次数: 0

摘要

系统性红斑狼疮是一种自身免疫性疾病,会导致免疫介导的肾脏和其他器官损伤。我们研究了补体32反应基因(RGC-32)在肾毒性肾炎(NTN)中的作用,肾毒性肾炎是一种模拟人类狼疮肾炎的实验模型。RGC-32 KO NTN 小鼠的蛋白尿、肾功能丧失和肾组织病理学均有所减轻。RGC-32 KO NTN小鼠的CCL20/CCR6和CXCL9/CXCR3配体/受体对出现下调,导致IL-17+和IFNγ+细胞的肾脏招募减少,先天性免疫细胞的流入也随之减少。RGC-32 缺乏会减轻肾脏纤维化,这表现在胶原蛋白 I、III 和纤维连接蛋白的沉积减少。因此,RGC-32 是 Th17 和 Th1 依赖性促炎和促纤维化途径共有的一种独特介质,是治疗免疫复合物介导的肾小球肾炎(如狼疮性肾炎)的潜在新治疗靶点。
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RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease

Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17+ and IFNγ+ cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. Thus, RGC-32 is a unique mediator shared by the Th17 and Th1 dependent proinflammatory and profibrotic pathways and a potential novel therapeutic target in the treatment of immune complex mediated glomerulonephritis such as lupus nephritis.

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来源期刊
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
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