Pub Date : 2025-12-16DOI: 10.1038/s41590-025-02402-5
Kevin Mulder, Margaux Gardet, Wan Ting Kong, Amit Ashok Patel, Anne Calvez, Grégoire Gessain, Carlos de la Calle-Fabregat, Cécile Piot, Quentin Blampey, Elisa Poupaud, Ahmed-Amine Anzali, Garett Dunsmore, Antoine Bougouin, Guilhem Pupier, Lizhe He, Timothy Wiggins, Jiang He, George Emanuel, Anne-Gaëlle Goubet, Ghamdan Al-Eryani, Alexander Swarbrick, Judith Michels, Regine J Dress, Marc Deloger, Antonio Bertoletti, Vincent Thomas de Montpreville, Catherine Sautès-Fridman, Wolf H Fridman, Laurence Zitvogel, Florent Ginhoux, Charles-Antoine Dutertre
{"title":"Author Correction: DC subsets and states unraveled across human juxtatumoral and malignant tissues.","authors":"Kevin Mulder, Margaux Gardet, Wan Ting Kong, Amit Ashok Patel, Anne Calvez, Grégoire Gessain, Carlos de la Calle-Fabregat, Cécile Piot, Quentin Blampey, Elisa Poupaud, Ahmed-Amine Anzali, Garett Dunsmore, Antoine Bougouin, Guilhem Pupier, Lizhe He, Timothy Wiggins, Jiang He, George Emanuel, Anne-Gaëlle Goubet, Ghamdan Al-Eryani, Alexander Swarbrick, Judith Michels, Regine J Dress, Marc Deloger, Antonio Bertoletti, Vincent Thomas de Montpreville, Catherine Sautès-Fridman, Wolf H Fridman, Laurence Zitvogel, Florent Ginhoux, Charles-Antoine Dutertre","doi":"10.1038/s41590-025-02402-5","DOIUrl":"10.1038/s41590-025-02402-5","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768397","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}
Pub Date : 2025-12-12DOI: 10.1038/s41590-025-02353-x
Malika Aid,Valentin Boero-Teyssier,Katherine McMahan,Rammy Dong,Michael Doyle,Nazim Belabbaci,Erica Borducchi,Ai-Ris Y Collier,Janet Mullington,Dan H Barouch
Long COVID (LC) involves a spectrum of chronic symptoms after acute severe acute respiratory syndrome coronavirus 2 infection. Current hypotheses for the pathogenesis of LC include persistent virus, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction and complement activation. We performed immunological, virological, transcriptomic and proteomic analyses from a cohort of 142 individuals between 2020 and 2021, including uninfected controls (n = 35), acutely infected individuals (n = 54), convalescent controls (n = 24) and patients with LC (n = 28). The LC group was characterized by persistent immune activation and proinflammatory responses for more than 180 days after initial infection compared with convalescent controls, including upregulation of JAK-STAT, interleukin-6, complement, metabolism and T cell exhaustion pathways. Similar findings were observed in a second cohort enrolled between 2023 and 2024, including convalescent controls (n = 20) and patients with LC (n = 18). These data suggest that LC is characterized by persistent activation of chronic inflammatory pathways, suggesting new therapeutic targets and potential biomarkers of disease.
{"title":"Long COVID involves activation of proinflammatory and immune exhaustion pathways.","authors":"Malika Aid,Valentin Boero-Teyssier,Katherine McMahan,Rammy Dong,Michael Doyle,Nazim Belabbaci,Erica Borducchi,Ai-Ris Y Collier,Janet Mullington,Dan H Barouch","doi":"10.1038/s41590-025-02353-x","DOIUrl":"https://doi.org/10.1038/s41590-025-02353-x","url":null,"abstract":"Long COVID (LC) involves a spectrum of chronic symptoms after acute severe acute respiratory syndrome coronavirus 2 infection. Current hypotheses for the pathogenesis of LC include persistent virus, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction and complement activation. We performed immunological, virological, transcriptomic and proteomic analyses from a cohort of 142 individuals between 2020 and 2021, including uninfected controls (n = 35), acutely infected individuals (n = 54), convalescent controls (n = 24) and patients with LC (n = 28). The LC group was characterized by persistent immune activation and proinflammatory responses for more than 180 days after initial infection compared with convalescent controls, including upregulation of JAK-STAT, interleukin-6, complement, metabolism and T cell exhaustion pathways. Similar findings were observed in a second cohort enrolled between 2023 and 2024, including convalescent controls (n = 20) and patients with LC (n = 18). These data suggest that LC is characterized by persistent activation of chronic inflammatory pathways, suggesting new therapeutic targets and potential biomarkers of disease.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"29 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732682","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}
Pub Date : 2025-12-12DOI: 10.1038/s41590-025-02379-1
Seok-Rae Park, Hong Zan, Zsuzsanna Pal, Jinsong Zhang, Ahmed Al-Qahtani, Egest J Pone, Zhenming Xu, Thach Mai, Paolo Casali
{"title":"Editorial Expression of Concern: HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation.","authors":"Seok-Rae Park, Hong Zan, Zsuzsanna Pal, Jinsong Zhang, Ahmed Al-Qahtani, Egest J Pone, Zhenming Xu, Thach Mai, Paolo Casali","doi":"10.1038/s41590-025-02379-1","DOIUrl":"https://doi.org/10.1038/s41590-025-02379-1","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743411","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}
Pub Date : 2025-12-08DOI: 10.1038/s41590-025-02337-x
Kevin Mulder,Margaux Gardet,Wan Ting Kong,Amit Ashok Patel,Anne Calvez,Grégoire Gessain,Carlos de la Calle-Fabregat,Cécile Piot,Quentin Blampey,Elisa Poupaud,Ahmed-Amine Anzali,Garett Dunsmore,Antoine Bougouin,Guilhem Pupier,Lizhe He,Timothy Wiggins,Jiang He,George Emanuel,Anne-Gaëlle Goubet,Ghamdan Al-Eryani,Alexander Swarbrick,Judith Michels,Regine J Dress,Marc Deloger,Antonio Bertoletti,Vincent Thomas de Montpreville,Catherine Sautès-Fridman,Wolf H Fridman,Laurence Zitvogel,Florent Ginhoux,Charles-Antoine Dutertre
Dendritic cells (DCs) are professional antigen-presenting cells. While plasmacytoid DCs (pDCs) are poor antigen-presenting cells at steady state, myeloid DCs (mDCs), which include DC1s, DC2s and DC3s, are specialized in T cell priming. To generate unbiased human DC atlases, we integrated DCs from 13 tumor tissues across 40 datasets to create a pDC + mDC-VERSE (DC-VERSE) and an mDC-VERSE single-cell RNA-sequencing compendium. We characterized DC subsets and 'states' across these tissues. Most studied tumors contained CD207+ DCs, a subset of CD1c+ DCs, whose expansion inversely correlated with tumor CD8+ resident memory T cells, T cell clonality and the survival of patients treated with immune checkpoint inhibitors. Similarly to CCR7+ mDCs (a common state of DC1s, DC2s and DC3s), we found that CD207+ DCs were a common state of DC2s and DC3s. Spatially resolved single-cell transcriptomic and immunohistofluorescence analyses of human carcinomas demonstrated that lymphocytes and most DCs were enriched within the tumor stroma, while CD207+ DCs were mostly embedded within tumor nests. These DC-VERSEs provide a robust resource available to the scientific community on DCs in health and pathology.
{"title":"DC subsets and states unraveled across human juxtatumoral and malignant tissues.","authors":"Kevin Mulder,Margaux Gardet,Wan Ting Kong,Amit Ashok Patel,Anne Calvez,Grégoire Gessain,Carlos de la Calle-Fabregat,Cécile Piot,Quentin Blampey,Elisa Poupaud,Ahmed-Amine Anzali,Garett Dunsmore,Antoine Bougouin,Guilhem Pupier,Lizhe He,Timothy Wiggins,Jiang He,George Emanuel,Anne-Gaëlle Goubet,Ghamdan Al-Eryani,Alexander Swarbrick,Judith Michels,Regine J Dress,Marc Deloger,Antonio Bertoletti,Vincent Thomas de Montpreville,Catherine Sautès-Fridman,Wolf H Fridman,Laurence Zitvogel,Florent Ginhoux,Charles-Antoine Dutertre","doi":"10.1038/s41590-025-02337-x","DOIUrl":"https://doi.org/10.1038/s41590-025-02337-x","url":null,"abstract":"Dendritic cells (DCs) are professional antigen-presenting cells. While plasmacytoid DCs (pDCs) are poor antigen-presenting cells at steady state, myeloid DCs (mDCs), which include DC1s, DC2s and DC3s, are specialized in T cell priming. To generate unbiased human DC atlases, we integrated DCs from 13 tumor tissues across 40 datasets to create a pDC + mDC-VERSE (DC-VERSE) and an mDC-VERSE single-cell RNA-sequencing compendium. We characterized DC subsets and 'states' across these tissues. Most studied tumors contained CD207+ DCs, a subset of CD1c+ DCs, whose expansion inversely correlated with tumor CD8+ resident memory T cells, T cell clonality and the survival of patients treated with immune checkpoint inhibitors. Similarly to CCR7+ mDCs (a common state of DC1s, DC2s and DC3s), we found that CD207+ DCs were a common state of DC2s and DC3s. Spatially resolved single-cell transcriptomic and immunohistofluorescence analyses of human carcinomas demonstrated that lymphocytes and most DCs were enriched within the tumor stroma, while CD207+ DCs were mostly embedded within tumor nests. These DC-VERSEs provide a robust resource available to the scientific community on DCs in health and pathology.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"13 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704707","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}
The anatomical source of infection is a major determinant of sepsis outcomes; however, how distinct sites shape immunity remains unclear. Here we applied multi-omic profiling, integrating single-cell transcriptomics, single-cell T cell receptor and B cell receptor sequencing, CITE-seq, bulk RNA sequencing and plasma proteomics, to analyze peripheral blood mononuclear cells and plasma from 281 adult and pediatric individuals with sepsis and controls. We identified an NR4A2+ central memory CD4+ T cell subset enriched in abdominal, pulmonary and skin sepsis, with features of exhaustion; genetic perturbations showed Nr4a2 loss improved survival, while overexpression worsened it. Proinflammatory CD8+ T, natural killer and natural killer T subsets expressing CCL4, CCL3 and tumor necrosis factor expanded in adult abdominal and pulmonary sepsis, while pediatric pulmonary sepsis featured proliferative CD14+ monocytes, findings validated in external single-cell cohorts and confirmed in 164 independent individuals. Plasma proteomics revealed shared mediators including interleukin-6 and EN-RAGE across anatomical sites and ages. Together, our findings delineate anatomical-specific and age-specific immune programs in sepsis, highlighting candidate targets for precision immunotherapy.
{"title":"Single-cell multi-omic landscape reveals anatomical-specific immune features in adult and pediatric sepsis.","authors":"Qian Ye,Xiaofei Lai,Yuliang Liu,Zhengtao Zhang,Yueqiang Fu,Jie Luo,Chengjun Liu,Jun Duan,Hao Ding,Yuhan Liu,Zhi Ao,Yang Tao,Shanmu Ai,Wei Huang,Lei Jiang,Yi Liu,Fang Xu,Ju Cao","doi":"10.1038/s41590-025-02345-x","DOIUrl":"https://doi.org/10.1038/s41590-025-02345-x","url":null,"abstract":"The anatomical source of infection is a major determinant of sepsis outcomes; however, how distinct sites shape immunity remains unclear. Here we applied multi-omic profiling, integrating single-cell transcriptomics, single-cell T cell receptor and B cell receptor sequencing, CITE-seq, bulk RNA sequencing and plasma proteomics, to analyze peripheral blood mononuclear cells and plasma from 281 adult and pediatric individuals with sepsis and controls. We identified an NR4A2+ central memory CD4+ T cell subset enriched in abdominal, pulmonary and skin sepsis, with features of exhaustion; genetic perturbations showed Nr4a2 loss improved survival, while overexpression worsened it. Proinflammatory CD8+ T, natural killer and natural killer T subsets expressing CCL4, CCL3 and tumor necrosis factor expanded in adult abdominal and pulmonary sepsis, while pediatric pulmonary sepsis featured proliferative CD14+ monocytes, findings validated in external single-cell cohorts and confirmed in 164 independent individuals. Plasma proteomics revealed shared mediators including interleukin-6 and EN-RAGE across anatomical sites and ages. Together, our findings delineate anatomical-specific and age-specific immune programs in sepsis, highlighting candidate targets for precision immunotherapy.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"198200 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664015","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}
Pub Date : 2025-12-01DOI: 10.1038/s41590-025-02380-8
Manuel A Sanchez-Garcia, Pranvera Sadiku, Brian M Ortmann, Niek Wit, Yutaka Negishi, Patricia Coelho, Ailiang Zhang, Chinmayi Pednekar, Andrew J M Howden, David M Griffith, Rachel Seear, Jessica D Kindrick, Janine Mengede, George Cooper, Tyler Morrison, Emily R Watts, Benjamin T Shimeld, Leila Reyes, Ananda S Mirchandani, Simone Arienti, Xiang Xu, Alexander Thomson, Alejandro J Brenes, Helena A Turton, Rebecca Dowey, Rebecca C Hull, Hazel Davidson-Smith, Amy McLaren, Andrew Deans, Gourab Choudhury, Katherine Doverman, David Hope, Oliver Vick, Alastair Woodhead, Isla Petrie, Suzanne Green, Nina M Rzechorzek, Lance Turtle, Peter J M Openshaw, Malcolm G Semple, Duncan Sproul, J Kenneth Baillie, Alfred A R Thompson, David R Mole, Alex von Kriegsheim, Moira K B Whyte, Musa M Mhlanga, James A Nathan, Sarah R Walmsley
{"title":"Author Correction: Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of neutrophil immunity.","authors":"Manuel A Sanchez-Garcia, Pranvera Sadiku, Brian M Ortmann, Niek Wit, Yutaka Negishi, Patricia Coelho, Ailiang Zhang, Chinmayi Pednekar, Andrew J M Howden, David M Griffith, Rachel Seear, Jessica D Kindrick, Janine Mengede, George Cooper, Tyler Morrison, Emily R Watts, Benjamin T Shimeld, Leila Reyes, Ananda S Mirchandani, Simone Arienti, Xiang Xu, Alexander Thomson, Alejandro J Brenes, Helena A Turton, Rebecca Dowey, Rebecca C Hull, Hazel Davidson-Smith, Amy McLaren, Andrew Deans, Gourab Choudhury, Katherine Doverman, David Hope, Oliver Vick, Alastair Woodhead, Isla Petrie, Suzanne Green, Nina M Rzechorzek, Lance Turtle, Peter J M Openshaw, Malcolm G Semple, Duncan Sproul, J Kenneth Baillie, Alfred A R Thompson, David R Mole, Alex von Kriegsheim, Moira K B Whyte, Musa M Mhlanga, James A Nathan, Sarah R Walmsley","doi":"10.1038/s41590-025-02380-8","DOIUrl":"https://doi.org/10.1038/s41590-025-02380-8","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655159","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}
Pub Date : 2025-11-28DOI: 10.1038/s41590-025-02375-5
Srividya Swaminathan, Lars Klemm, Eugene Park, Elli Papaemmanuil, Anthony Ford, Soo-Mi Kweon, Daniel Trageser, Brian Hasselfeld, Nadine Henke, Jana Mooster, Huimin Geng, Klaus Schwarz, Scott C. Kogan, Rafael Casellas, David G. Schatz, Michael R. Lieber, Mel F. Greaves, Markus Müschen
{"title":"Author Correction: Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia","authors":"Srividya Swaminathan, Lars Klemm, Eugene Park, Elli Papaemmanuil, Anthony Ford, Soo-Mi Kweon, Daniel Trageser, Brian Hasselfeld, Nadine Henke, Jana Mooster, Huimin Geng, Klaus Schwarz, Scott C. Kogan, Rafael Casellas, David G. Schatz, Michael R. Lieber, Mel F. Greaves, Markus Müschen","doi":"10.1038/s41590-025-02375-5","DOIUrl":"https://doi.org/10.1038/s41590-025-02375-5","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"5 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611573","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}
Pub Date : 2025-11-28DOI: 10.1038/s41590-025-02343-z
Neetu Srivastava, Anthony N. Vomund, Rongzhen Yu, Orion J. Peterson, Yuqing Yang, David P. Turicek, Omar Abousaway, Tiandao Li, Lisa Kain, Pamela Stone, Aisha Ansar, Cristina C. Clement, Siddhartha Sharma, Rima Melhem, Bo Zhang, Chang Liu, Alok V. Joglekar, Hao Hu, Chyi-Song Hsieh, Laura Campisi, Laura Santambrogio, Luc Teyton, Emil R. Unanue, Ana Maria Arbelaez, Cheryl F. Lichti, Xiaoxiao Wan
{"title":"A microenvironment-driven HLA-II-associated insulin neoantigen elicits persistent memory T cell activation in diabetes","authors":"Neetu Srivastava, Anthony N. Vomund, Rongzhen Yu, Orion J. Peterson, Yuqing Yang, David P. Turicek, Omar Abousaway, Tiandao Li, Lisa Kain, Pamela Stone, Aisha Ansar, Cristina C. Clement, Siddhartha Sharma, Rima Melhem, Bo Zhang, Chang Liu, Alok V. Joglekar, Hao Hu, Chyi-Song Hsieh, Laura Campisi, Laura Santambrogio, Luc Teyton, Emil R. Unanue, Ana Maria Arbelaez, Cheryl F. Lichti, Xiaoxiao Wan","doi":"10.1038/s41590-025-02343-z","DOIUrl":"https://doi.org/10.1038/s41590-025-02343-z","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"255 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611572","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}
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