Nature Immunology最新文献

{"title":"Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bnAb for HIV-1 prevention and therapy.","authors":"Lutz Gieselmann, Andrew T DeLaitsch, Malena Rohde, Henning Gruell, Christoph Kreer, Meryem Seda Ercanoglu, Harry B Gristick, Philipp Schommers, Elvin Ahmadov, Caelan Radford, Andrea Mazzolini, Lily Zhang, Anthony P West, Johanna Worczinski, Anna Momot, Maren L Reichwein, Jacqueline Knüfer, Ricarda Stumpf, Nonhlanhla N Mkhize, Haajira Kaldine, Sinethemba Bhebhe, Sharvari Deshpande, Federico Giovannoni, Erin Stefanutti, Fabio Benigni, Colin Havenar-Daughton, Davide Corti, Arne Kroidl, Anurag Adhikari, Aubin J Nanfack, Georgia E Ambada, Ralf Duerr, Lucas Maganga, Wiston William, Nyanda E Ntinginya, Timo Wolf, Christof Geldmacher, Michael Hoelscher, Clara Lehmann, Penny L Moore, Thierry Mora, Aleksandra M Walczak, Peter B Gilbert, Nicole A Doria-Rose, Yunda Huang, Jesse D Bloom, Michael S Seaman, Pamela J Bjorkman, Florian Klein","doi":"10.1038/s41590-025-02286-5","DOIUrl":"10.1038/s41590-025-02286-5","url":null,"abstract":"<p><p>Administration of HIV-1 neutralizing antibodies can suppress viremia and prevent infection in vivo. However, clinical use is challenged by envelope diversity and rapid viral escape. Here, we performed single B cell profiling of 32 top HIV-1 elite neutralizers to identify broadly neutralizing antibodies with highest antiviral activity. From 831 expressed monoclonal antibodies, we identified 04_A06, a V_H1-2-encoded broadly neutralizing antibody to the CD4 binding site with remarkable breadth and potency against multiclade pseudovirus panels (geometric mean half-maximal inhibitory concentration = 0.059 µg ml^-1, breadth = 98.5%, 332 strains). Moreover, 04_A06 was not susceptible to classic CD4 binding site escape variants and maintained full viral suppression in HIV-1-infected humanized mice. Structural analyses revealed an unusually long 11-amino-acid heavy chain insertion that facilitates interprotomer contacts with highly conserved residues on the adjacent gp120 protomer. Finally, 04_A06 demonstrated high activity against contemporaneously circulating viruses from the Antibody-Mediated Prevention trials (geometric mean half-maximal inhibitory concentration = 0.082 µg ml^-1, breadth = 98.4%, 191 virus strains), and in silico modeling for 04_A06LS predicted prevention efficacy of >93%. Thus, 04_A06 will provide unique opportunities for effective treatment and prevention of HIV-1 infection.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ThymUS approaching maturity.","authors":"Marieke Lavaert, Susannah C Shissler, Avinash Bhandoola","doi":"10.1038/s41590-025-02296-3","DOIUrl":"https://doi.org/10.1038/s41590-025-02296-3","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"10.1038/s41590-025-02291-8","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":27.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy-induced CA-repeat DNA fragments in breast cancer trigger antitumor immune responses.","authors":"Xiaoqian Zhang,Penghan Huang,Huiping Chen,Chaoqun Yang,Xinyu Yang,Yujie Liu,Baixing Wu,Wenfeng Zeng,Phei Er Saw,Shuying Ye,Jiaqian Li,Jiayi Wang,Zizhen Wu,Jiawen Wang,Heliang Li,Jian-Dong Huang,Musheng Zeng,Mengfeng Li,Qiang Liu,Shicheng Su,Erwei Song,Jianing Chen","doi":"10.1038/s41590-025-02289-2","DOIUrl":"https://doi.org/10.1038/s41590-025-02289-2","url":null,"abstract":"Damage-associated molecular patterns generated by cancer treatment can modulate antitumor immunity, but the underlying mechanisms of this effect are unclear. Here we show that CA-enriched DNA fragments resulting from DNA-damaging chemotherapy in MSH2-low tumors preferentially bind cGAS with strong affinity and form biomolecular condensates by phase separation in the cytoplasm, resulting in antitumor immunity. However, classical CA-poor DNAs released from MSH2-high tumor cells engage AIM2, resulting in immunosuppression by upregulating PD-L1 and IDO. Intratumoral administration of CA-rich DNA fragments enhanced antitumor immunity in syngrafted PyMT tumors. Clinically, CA-rich DNA abundance in breast cancer following chemotherapy was associated with increased tumor-antigen-reactive T cells and better chemotherapeutic responses. Therefore, different tumor DNA fragments can trigger opposing immune responses depending on their preference for differential sensors. This study highlights another mechanistic link between genome instability and immune modulation and the therapeutic potential of CA-rich DNAs to enhance antitumor immunity.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"28 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effector-memory ILC2s","authors":"Paula Jauregui","doi":"10.1038/s41590-025-02304-6","DOIUrl":"10.1038/s41590-025-02304-6","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1627-1627"},"PeriodicalIF":27.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages drive fat cell differentiation","authors":"Stephanie Houston","doi":"10.1038/s41590-025-02305-5","DOIUrl":"10.1038/s41590-025-02305-5","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1627-1627"},"PeriodicalIF":27.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evading tumor evasion","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-025-02303-7","DOIUrl":"10.1038/s41590-025-02303-7","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1627-1627"},"PeriodicalIF":27.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections.","authors":"Clemence Ngo, Camille Pierini-Malosse, Khalissa Rahmani, Michael Valente, Nils Collinet, Gilles Bessou, Capucine Guerry, Manon Fabregue, Solene Mathieu, Sarah Sharkaoui, Sophie Mazzoli, Amandine Sansoni, Frederic Fiore, Caroline Laprie, Lena Alexopoulou, Mauro Gaya, Claude Gregoire, Achille Broggi, Sarah Wurbel, Réjane Rua, Narjess Haidar, Pierre Milpied, Bertrand Escalière, Thien Phong Vu Manh, Mathieu Fallet, Lionel Chasson, Hien Tran, Thomas Baranek, Marc Le Bert, Bernard Malissen, Ana Zarubica, Marc Dalod, Elena Tomasello","doi":"10.1038/s41590-025-02288-3","DOIUrl":"10.1038/s41590-025-02288-3","url":null,"abstract":"<p><p>Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process; however, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDCs or disrupt their interferon production often affect other cells, confounding interpretation. Here, to overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the Siglech and Pacsin1 genes, uniquely coexpressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse cytomegalovirus and showed higher survival and less lung immunopathology to intranasal infection with influenza virus and SARS-CoV-2. Thus, contrary to the prevailing dogma, we revealed that pDCs and their interferons are dispensable or deleterious during several viral infections. pDC-less mice will enable rigorously reassessing the roles of pDCs in health and disease.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensory nerve niches","authors":"Ioana Staicu","doi":"10.1038/s41590-025-02302-8","DOIUrl":"10.1038/s41590-025-02302-8","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1627-1627"},"PeriodicalIF":27.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV-induced T cell quiescence and the origins of viral latency","authors":"Zichong Li,&nbsp;Melanie Ott","doi":"10.1038/s41590-025-02282-9","DOIUrl":"10.1038/s41590-025-02282-9","url":null,"abstract":"HIV drives host cells into dormancy within days of infection, actively laying the groundwork for latency and long-term persistence.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1633-1634"},"PeriodicalIF":27.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}