自身免疫性肾病中免疫细胞和肾细胞的时空相互作用控制肾小球新月形成。

IF 27.6 1区 医学 Q1 IMMUNOLOGY
Zeba Sultana, Robin Khatri, Behnam Yousefi, Nikhat Shaikh, Saskia L Jauch-Speer, Darius P Schaub, Jonas Engesser, Malte Hellmig, Vincent Piegsa, Arthur Hube, Varshi Sivayoganathan, Alina Borchers, Anett Peters, Anna Kaffke, Stephanie Zielinski, Hans-Joachim Paust, Thiago Goldbeck-Strieder, Ulrich O Wenzel, Victor G Puelles, Elion Hoxha, Thorsten Wiech, Catherine Meyer-Schwesinger, Tobias B Huber, Ulf Panzer, Stefan Bonn, Christian F Krebs
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引用次数: 0

摘要

快速进行性肾小球肾炎(RPGN)是自身免疫性肾脏疾病中最具侵袭性的一组,其特征是肾小球呈新月形形成并伴有壁上皮细胞(PECs)的增殖。然而,肾小球新月形成的潜在机制尚不完全清楚。在这里,我们提供了来自RPGN (anca相关的GN,狼疮肾炎和抗肾小球基底膜-GN)患者的57个样本的高分辨率空间肾细胞图谱,以表征肾小球新月发展中的细胞信号通路。来自上皮细胞和系膜细胞的早期血小板衍生生长因子(PDGF)信号导致肾小球月牙形中PEC的激活和增殖,而来自巨噬细胞、T细胞和上皮细胞和系膜细胞的晚期转化生长因子(TGF)-β信号触发与肾小球硬化和疾病进展相关的PECs细胞外基质成分的表达。这些发现在不同的GN中是相似的,并且通过PDGF和TGFβ阻断在实验性GN中得到了功能验证。这些结果强调了一个时空保守的肾小球新月形和硬化进展程序,并提示了自身免疫性肾脏疾病的新治疗选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Spatiotemporal interaction of immune and renal cells controls glomerular crescent formation in autoimmune kidney disease.

Rapidly progressive glomerulonephritis (RPGN) is the most aggressive group of autoimmune kidney diseases and is characterized by glomerular crescent formation with proliferation of parietal epithelial cells (PECs). However, the underlying mechanisms of glomerular crescent formation are incompletely understood. Here we provide a high-resolution spatial kidney cell atlas of 57 samples from patients with RPGN (ANCA-associated GN, lupus nephritis and anti-glomerular basement membrane-GN) to characterize the cell signaling pathways in glomerular crescent development. Early platelet-derived growth factor (PDGF) signaling from epithelial and mesangial cells caused PEC activation and proliferation in glomerular crescents, whereas later transforming growth factor (TGF)-β signaling from macrophages, T cells and epithelial and mesangial cells triggered expression of extracellular matrix components in PECs associated with glomerulosclerosis and disease progression. These findings were similar across the different GNs and were functionally validated in experimental GN by PDGF and TGFβ blockade. These results highlight a spatiotemporally conserved progression program into glomerular crescents and sclerosis and indicate new treatment options for autoimmune kidney disease.

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来源期刊
Nature Immunology
Nature Immunology 医学-免疫学
CiteScore
40.00
自引率
2.30%
发文量
248
审稿时长
4-8 weeks
期刊介绍: Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
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