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
{"title":"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。","authors":"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","doi":"10.1038/s41590-025-02291-8","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Spatiotemporal interaction of immune and renal cells controls glomerular crescent formation in autoimmune kidney disease.\",\"authors\":\"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\",\"doi\":\"10.1038/s41590-025-02291-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":19032,\"journal\":{\"name\":\"Nature Immunology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":27.6000,\"publicationDate\":\"2025-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41590-025-02291-8\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41590-025-02291-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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.