Pub Date : 2025-12-05DOI: 10.1126/sciimmunol.aea8735
Jacob Kim, Ao Huang, John S. Tsang
Large language model (LLM)–based artificial intelligence (AI) agents are powerful tools that can help researchers automate complex tasks such as literature review, data mining, computational code generation, and summarization of existing knowledge, but they can still fall short in developing original biological hypotheses and insights (see related Research Article by Rodriguez-Coffinet et al. in this issue). Emerging advances in multiagent systems and human-agent collaborative frameworks offer promising steps forward.
基于大型语言模型（LLM）的人工智能（AI）代理是一种强大的工具，可以帮助研究人员自动完成复杂的任务，如文献综述、数据挖掘、计算代码生成和现有知识的总结，但它们在开发原始生物学假设和见解方面仍然存在不足（参见Rodriguez-Coffinet et al.在本期的相关研究文章）。多智能体系统和人类智能体协作框架的新进展提供了有希望的进步。
{"title":"AI immunologists are here: Are they ready for prime time?","authors":"Jacob Kim, Ao Huang, John S. Tsang","doi":"10.1126/sciimmunol.aea8735","DOIUrl":"10.1126/sciimmunol.aea8735","url":null,"abstract":"<div >Large language model (LLM)–based artificial intelligence (AI) agents are powerful tools that can help researchers automate complex tasks such as literature review, data mining, computational code generation, and summarization of existing knowledge, but they can still fall short in developing original biological hypotheses and insights (see related Research Article by Rodriguez-Coffinet <i>et al.</i> in this issue). Emerging advances in multiagent systems and human-agent collaborative frameworks offer promising steps forward.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 114","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674552","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: 10.1126/sciimmunol.adz4626
Elisabeth De Leeuw, Josefine F. Justesen, Cédric Bosteels, Nincy Debeuf, Manon Vanheerswynghels, Leander Jonckheere, Caroline De Wolf, Alysia Wayenberg, Karel F.A. Van Damme, Stijn Vanhee, Manon Lesage, Kim Deswarte, Sam Dupont, Morten Dahl, Hamida Hammad, Bart N. Lambrecht
Allergic asthma arises from complex genetic and environmental interactions. Analysis of a population-wide registry revealed that infants hospitalized for human respiratory syncytial virus (RSV) bronchiolitis who are born to asthmatic parents have a markedly increased risk of developing asthma. To model this interaction, neonatal mice infected with pneumonia virus of mice (PVM), an RSV analog, before house dust mite (HDM) exposure developed amplified type 2 inflammation and asthma-like pathology. Maternal, but not paternal, HDM allergy intensified disease, implicating vertical transmission of an immune risk factor. Mechanistically, neonatal viral infection up-regulated Fc receptors (FcRs) and promoted maturation of type 2 conventional dendritic cells (cDC2s). Maternal allergen-specific immunoglobulin G (IgG), transferred via neonatal Fc receptor (FcRn), enhanced Fc gamma receptor (FcγR)–mediated allergen uptake and T helper 2 (TH2) cell priming. Preventive RSV immunoprophylaxis blocked asthma development in this setting. These findings identify maternal allergy and neonatal RSV infection as converging FcR-dependent causal asthma risk factors, preventable through immunoprophylaxis.
{"title":"Maternal allergy and neonatal RSV infection synergize via FcR-mediated allergen uptake to promote the development of asthma in early life","authors":"Elisabeth De Leeuw, Josefine F. Justesen, Cédric Bosteels, Nincy Debeuf, Manon Vanheerswynghels, Leander Jonckheere, Caroline De Wolf, Alysia Wayenberg, Karel F.A. Van Damme, Stijn Vanhee, Manon Lesage, Kim Deswarte, Sam Dupont, Morten Dahl, Hamida Hammad, Bart N. Lambrecht","doi":"10.1126/sciimmunol.adz4626","DOIUrl":"10.1126/sciimmunol.adz4626","url":null,"abstract":"<div >Allergic asthma arises from complex genetic and environmental interactions. Analysis of a population-wide registry revealed that infants hospitalized for human respiratory syncytial virus (RSV) bronchiolitis who are born to asthmatic parents have a markedly increased risk of developing asthma. To model this interaction, neonatal mice infected with pneumonia virus of mice (PVM), an RSV analog, before house dust mite (HDM) exposure developed amplified type 2 inflammation and asthma-like pathology. Maternal, but not paternal, HDM allergy intensified disease, implicating vertical transmission of an immune risk factor. Mechanistically, neonatal viral infection up-regulated Fc receptors (FcRs) and promoted maturation of type 2 conventional dendritic cells (cDC2s). Maternal allergen-specific immunoglobulin G (IgG), transferred via neonatal Fc receptor (FcRn), enhanced Fc gamma receptor (FcγR)–mediated allergen uptake and T helper 2 (T<sub>H</sub>2) cell priming. Preventive RSV immunoprophylaxis blocked asthma development in this setting. These findings identify maternal allergy and neonatal RSV infection as converging FcR-dependent causal asthma risk factors, preventable through immunoprophylaxis.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 113","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adz4626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-21DOI: 10.1126/sciimmunol.aed4813
Seth Thomas Scanlon
{"title":"Editorial expression of concern","authors":"Seth Thomas Scanlon","doi":"10.1126/sciimmunol.aed4813","DOIUrl":"10.1126/sciimmunol.aed4813","url":null,"abstract":"","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 113","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561891","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 : 2025-11-21DOI: 10.1126/sciimmunol.adz0472
Maryam Abedi, Priyadarshini Rai, Yeqiao Zhou, Chengyang Liu, Isabelle Johnson, Aditi Chandra, Maria Fasolino, Susan Rostami, Wei Wang, Zaw Min, Yanjing Li, Ming Yu, Atishay Jay, Vung Lian, Michael Silverman, Klaus H. Kaestner, Ali Naji, Robert B. Faryabi, Golnaz Vahedi
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β cells in the pancreas. While current therapies focus on managing the disease, a deeper understanding of the underlying molecular mechanisms is crucial for developing disease-modifying interventions. In this study, we conducted a comprehensive analysis of gene expression and chromatin accessibility in nearly 1 million immune cells from the pancreatic lymph nodes and spleens of 43 individuals with and without T1D. We found a distinct subset of CD4 T cells specifically present in the pancreatic lymph nodes of organ donors representing the active disease stage. These cells exhibited elevated activity of NFKB1 and BACH2, along with extensive chromatin remodeling associated with these transcription factors, which we also corroborated in a mouse model of T1D. A better understanding of these NFKB1-BACH2–expressing CD4 T cells may lead to therapeutic avenues for preventing or delaying T1D onset.
{"title":"Joint profiling of gene expression and chromatin accessibility in pancreatic lymph nodes and spleens in human type 1 diabetes","authors":"Maryam Abedi, Priyadarshini Rai, Yeqiao Zhou, Chengyang Liu, Isabelle Johnson, Aditi Chandra, Maria Fasolino, Susan Rostami, Wei Wang, Zaw Min, Yanjing Li, Ming Yu, Atishay Jay, Vung Lian, Michael Silverman, Klaus H. Kaestner, Ali Naji, Robert B. Faryabi, Golnaz Vahedi","doi":"10.1126/sciimmunol.adz0472","DOIUrl":"10.1126/sciimmunol.adz0472","url":null,"abstract":"<div >Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β cells in the pancreas. While current therapies focus on managing the disease, a deeper understanding of the underlying molecular mechanisms is crucial for developing disease-modifying interventions. In this study, we conducted a comprehensive analysis of gene expression and chromatin accessibility in nearly 1 million immune cells from the pancreatic lymph nodes and spleens of 43 individuals with and without T1D. We found a distinct subset of CD4 T cells specifically present in the pancreatic lymph nodes of organ donors representing the active disease stage. These cells exhibited elevated activity of <i>NFKB1</i> and <i>BACH2</i>, along with extensive chromatin remodeling associated with these transcription factors, which we also corroborated in a mouse model of T1D. A better understanding of these <i>NFKB1-BACH2</i>–expressing CD4 T cells may lead to therapeutic avenues for preventing or delaying T1D onset.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 113","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adz0472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-21DOI: 10.1126/sciimmunol.adu2089
Han Feng, Sungjun Park, Jae Woo Shin, Francisco Emmanuel Castañeda-Castro, Job Rocha Hernandez, Benjamin J. Schmiedel, Changlu Liu, Michael R. Jackson, Christian H. Ottensmeier, Pandurangan Vijayanand
Tissue-resident memory CD8 T (TRM) cells provide critical antiviral and antitumor immunity, but the molecular pathways guiding their development are not fully defined. Here, we identify the G protein–coupled receptor GPR25, induced by TGF-β signaling, as a regulator of TRM cell formation. Using adoptive transfer, we found that Gpr25-deficient T cells infiltrated tissues normally after viral infection but failed to efficiently develop into TRM cells. In a tumor challenge model, Gpr25 deficiency impaired TRM cell expansion and tumor control. Single-cell transcriptomics revealed defective acquisition of stem-like TRM cell features, including expression of T cell factor 1 (TCF1). After antigen rechallenge, Gpr25-deficient TRM cells showed impaired secondary TRM cell differentiation and maintenance. Moreover, Gpr25-deficient T cells displayed negative enrichment of TGF-β signature genes and impaired responses to TGF-β, indicating that GPR25 enhances TGF-β signaling to promote TRM cell development. Our findings suggest that modulating GPR25 function may provide a therapeutic strategy to improve TRM cell responses in infection and cancer.
{"title":"GPR25 promotes the formation of lung and liver tissue-resident memory CD8 T cells","authors":"Han Feng, Sungjun Park, Jae Woo Shin, Francisco Emmanuel Castañeda-Castro, Job Rocha Hernandez, Benjamin J. Schmiedel, Changlu Liu, Michael R. Jackson, Christian H. Ottensmeier, Pandurangan Vijayanand","doi":"10.1126/sciimmunol.adu2089","DOIUrl":"10.1126/sciimmunol.adu2089","url":null,"abstract":"<div >Tissue-resident memory CD8 T (T<sub>RM</sub>) cells provide critical antiviral and antitumor immunity, but the molecular pathways guiding their development are not fully defined. Here, we identify the G protein–coupled receptor GPR25, induced by TGF-β signaling, as a regulator of T<sub>RM</sub> cell formation. Using adoptive transfer, we found that <i>Gpr25</i>-deficient T cells infiltrated tissues normally after viral infection but failed to efficiently develop into T<sub>RM</sub> cells. In a tumor challenge model, <i>Gpr25</i> deficiency impaired T<sub>RM</sub> cell expansion and tumor control. Single-cell transcriptomics revealed defective acquisition of stem-like T<sub>RM</sub> cell features, including expression of T cell factor 1 (TCF1). After antigen rechallenge, <i>Gpr25</i>-deficient T<sub>RM</sub> cells showed impaired secondary T<sub>RM</sub> cell differentiation and maintenance. Moreover, <i>Gpr25</i>-deficient T cells displayed negative enrichment of TGF-β signature genes and impaired responses to TGF-β, indicating that GPR25 enhances TGF-β signaling to promote T<sub>RM</sub> cell development. Our findings suggest that modulating GPR25 function may provide a therapeutic strategy to improve T<sub>RM</sub> cell responses in infection and cancer.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 113","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559340","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 : 2025-11-14DOI: 10.1126/sciimmunol.ads8226
Danni Y. Zhu, Daniel P. Maurer, Carlos Castrillon, Yixiang Deng, Faez A. N. Mohamed, Minghe Ma, David Tang, Jessica Min-Debartolo, Nathan Higginson-Scott, Janet Buhlmann, Aaron G. Schmidt, Daniel Lingwood, Michael C. Carroll
The extrafollicular (EF) B cell differentiation pathway has emerged as a prominent source of autoantibody-secreting cells (ASCs) in systemic lupus erythematosus (SLE). CD21loCD11c+ B cells are associated with aging, infection, and autoimmunity. They are key contributors to EF ASCs, yet their developmental trajectory and receptor programming are unclear. To study EF mechanics of autoreactive B cells, we adoptively transferred naïve B cell populations into 564Igi mice, which act as an autoreactive host enriched for autoantigens and T cell help. Time-resolved analyses revealed a Toll-like receptor 7 (TLR7)–dependent early escape of peripheral tolerance and a pre–ASC division program. We identified naïve-derived CD21lo cells as precursors of EF ASCs exhibiting elevated reliance on TLR7. Repertoire analysis delineated protoautoreactive B cell selection and receptor evolution toward self-reactivity. Continuous complement receptor 2 (CR2/CD21)–complement C3d and CD21–complement iC3b engagement triggered receptor down-regulation before proliferation. We reveal CD21 as an initiator of TLR7-dependent autoimmune EF proliferation and target for suppressing autoreactivity.
{"title":"CD21 primes extrafollicular differentiation of autoreactive B cells in a TLR7-driven lupus model","authors":"Danni Y. Zhu, Daniel P. Maurer, Carlos Castrillon, Yixiang Deng, Faez A. N. Mohamed, Minghe Ma, David Tang, Jessica Min-Debartolo, Nathan Higginson-Scott, Janet Buhlmann, Aaron G. Schmidt, Daniel Lingwood, Michael C. Carroll","doi":"10.1126/sciimmunol.ads8226","DOIUrl":"10.1126/sciimmunol.ads8226","url":null,"abstract":"<div >The extrafollicular (EF) B cell differentiation pathway has emerged as a prominent source of autoantibody-secreting cells (ASCs) in systemic lupus erythematosus (SLE). CD21<sup>lo</sup>CD11c<sup>+</sup> B cells are associated with aging, infection, and autoimmunity. They are key contributors to EF ASCs, yet their developmental trajectory and receptor programming are unclear. To study EF mechanics of autoreactive B cells, we adoptively transferred naïve B cell populations into 564Igi mice, which act as an autoreactive host enriched for autoantigens and T cell help. Time-resolved analyses revealed a Toll-like receptor 7 (TLR7)–dependent early escape of peripheral tolerance and a pre–ASC division program. We identified naïve-derived CD21<sup>lo</sup> cells as precursors of EF ASCs exhibiting elevated reliance on TLR7. Repertoire analysis delineated protoautoreactive B cell selection and receptor evolution toward self-reactivity. Continuous complement receptor 2 (CR2/CD21)–complement C3d and CD21–complement iC3b engagement triggered receptor down-regulation before proliferation. We reveal CD21 as an initiator of TLR7-dependent autoimmune EF proliferation and target for suppressing autoreactivity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 113","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145509425","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 : 2025-11-14DOI: 10.1126/sciimmunol.adz5181
Amélie Grosjean, Aude Jalon, Claire Leveau, Marc Diedisheim, David Alejandro Bejarano, Joyceline Cuenco, Kevin Mulder, Zhaoyuan Liu, Audrey Le Guernic, Marie-Laure Island, Jarne Walkiers, Gamze Ates, Clément Materne, Andreia Goncalves, Ivan Nemazanyy, Laura G. Baudrin, Sylvain Baulande, Martine Ropert, Jean-François Gautier, Ahmed Hamaï, Andreas Schlitzer, Florent Ginhoux, Ann Massie, Nicolas Venteclef, Elise Dalmas
Pancreatic islet-resident macrophages (IRMs) display an activated phenotype and contribute to islet development and remodeling, yet their origin, heterogeneity, and functional roles remain poorly understood. Using complementary fate-mapping systems, we show that, in adult mice, around half of IRMs originate from circulating monocytes and undergo minimal turnover. Integrated multiple single-cell RNA sequencing analyses of mouse and human islets identified four major IRM cell states that collectively reveal their inflammatory and metabolic activation. Among these, a transcriptional program driven by the cystine-glutamate antiporter SLC7A11 and enriched in CD9high IRMs was associated with enhanced antioxidant defense, mitochondrial activity, and iron-lipid metabolic pathways. We found that Slc7a11-expressing IRMs preserve β cell redox homeostasis and insulin secretion, both at baseline and under stress. These findings position IRMs as specialized immune sentinels in the endocrine pancreas and identify SLC7A11 as a key macrophage-intrinsic safeguard against oxidative stress, with broad implications for islet resilience and metabolic health.
{"title":"An islet-resident macrophage antioxidant program preserves β cell physiology","authors":"Amélie Grosjean, Aude Jalon, Claire Leveau, Marc Diedisheim, David Alejandro Bejarano, Joyceline Cuenco, Kevin Mulder, Zhaoyuan Liu, Audrey Le Guernic, Marie-Laure Island, Jarne Walkiers, Gamze Ates, Clément Materne, Andreia Goncalves, Ivan Nemazanyy, Laura G. Baudrin, Sylvain Baulande, Martine Ropert, Jean-François Gautier, Ahmed Hamaï, Andreas Schlitzer, Florent Ginhoux, Ann Massie, Nicolas Venteclef, Elise Dalmas","doi":"10.1126/sciimmunol.adz5181","DOIUrl":"10.1126/sciimmunol.adz5181","url":null,"abstract":"<div >Pancreatic islet-resident macrophages (IRMs) display an activated phenotype and contribute to islet development and remodeling, yet their origin, heterogeneity, and functional roles remain poorly understood. Using complementary fate-mapping systems, we show that, in adult mice, around half of IRMs originate from circulating monocytes and undergo minimal turnover. Integrated multiple single-cell RNA sequencing analyses of mouse and human islets identified four major IRM cell states that collectively reveal their inflammatory and metabolic activation. Among these, a transcriptional program driven by the cystine-glutamate antiporter SLC7A11 and enriched in CD9<sup>high</sup> IRMs was associated with enhanced antioxidant defense, mitochondrial activity, and iron-lipid metabolic pathways. We found that <i>Slc7a11</i>-expressing IRMs preserve β cell redox homeostasis and insulin secretion, both at baseline and under stress. These findings position IRMs as specialized immune sentinels in the endocrine pancreas and identify SLC7A11 as a key macrophage-intrinsic safeguard against oxidative stress, with broad implications for islet resilience and metabolic health.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 113","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145509424","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 : 2025-11-07DOI: 10.1126/sciimmunol.aed4910
Kevin Champagne-Jorgensen, Jennifer L. Gommerman
An MS twin study links ileal Lachnospiraceae to spontaneous CNS autoimmunity in mice receiving a human microbiome transplant.
一项MS双胞胎研究将回肠毛缕菌科与接受人类微生物组移植的小鼠自发性中枢神经系统自身免疫联系起来。
{"title":"Two of a kind, one with MS: Gut microbes tip the balance","authors":"Kevin Champagne-Jorgensen, Jennifer L. Gommerman","doi":"10.1126/sciimmunol.aed4910","DOIUrl":"10.1126/sciimmunol.aed4910","url":null,"abstract":"<div >An MS twin study links ileal <i>Lachnospiraceae</i> to spontaneous CNS autoimmunity in mice receiving a human microbiome transplant.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 113","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455362","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}
Mammalian hematopoietic cells arise from mesodermal progenitors in a close developmental relationship with endothelium and along three distinct cell lineages known as primitive, prodefinitive, and definitive hematopoiesis. However, the developmental hierarchies between early mesodermal progenitors, endothelium, and blood cell lineages are incompletely understood. Here, fate-mapping, cloning, and genetic experiments identified a population of KDR+CXCR4+ prodefinitive angio-hematopoietic progenitors (PDAPs) in murine primitive streak stage mesoderm and human induced pluripotent stem cell (hiPSC) cultures. PDAPs gave rise to yolk sac (YS) and rostral (cephalic) endothelial cells and RUNX1-dependent prodefinitive hematopoietic cells, including erythro-myeloid progenitors (EMPs) and tissue macrophages, via NOTCH1-independent hemogenic endothelial cells. Notably, PDAPs did not give rise to primitive erythropoiesis or to caudal endothelium and definitive hematopoiesis. These results identify a previously unrecognized layer of lineage segregation in early mammalian mesoderm that characterizes the prodefinitive angio-hematopoietic lineage and the origin of tissue macrophages and rostral blood vessels that may be of interest for pathophysiology and cell-based therapy efforts.
{"title":"Characterization of the mammalian prodefinitive angio-hematopoietic lineage","authors":"Tomi Lazarov, Pierre-Louis Loyher, Hairu Yang, Zi-Ning Choo, Zihou Deng, Sonja Nowotschin, Ying-Yi Kuo, Ting Zhou, Araitz Alberdi-Gonzalez, Ralf Stumm, Elvira Mass, Elisa Gomez Perdiguero, Anna-Katerina Hadjantonakis, Frederic Geissmann","doi":"10.1126/sciimmunol.adt6616","DOIUrl":"10.1126/sciimmunol.adt6616","url":null,"abstract":"<div >Mammalian hematopoietic cells arise from mesodermal progenitors in a close developmental relationship with endothelium and along three distinct cell lineages known as primitive, prodefinitive, and definitive hematopoiesis. However, the developmental hierarchies between early mesodermal progenitors, endothelium, and blood cell lineages are incompletely understood. Here, fate-mapping, cloning, and genetic experiments identified a population of KDR<sup>+</sup>CXCR4<sup>+</sup> prodefinitive angio-hematopoietic progenitors (PDAPs) in murine primitive streak stage mesoderm and human induced pluripotent stem cell (hiPSC) cultures. PDAPs gave rise to yolk sac (YS) and rostral (cephalic) endothelial cells and RUNX1-dependent prodefinitive hematopoietic cells, including erythro-myeloid progenitors (EMPs) and tissue macrophages, via NOTCH1-independent hemogenic endothelial cells. Notably, PDAPs did not give rise to primitive erythropoiesis or to caudal endothelium and definitive hematopoiesis. These results identify a previously unrecognized layer of lineage segregation in early mammalian mesoderm that characterizes the prodefinitive angio-hematopoietic lineage and the origin of tissue macrophages and rostral blood vessels that may be of interest for pathophysiology and cell-based therapy efforts.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 113","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455427","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 : 2025-11-07DOI: 10.1126/sciimmunol.aed4909
Kritika Dixit, David R. Martinez
Repeated dengue infections elicit broadly neutralizing antibodies that are protective against severe disease.
反复的登革热感染引发广泛的中和抗体，对严重疾病具有保护作用。
{"title":"B cells and dengue: A cat-and-mouse game","authors":"Kritika Dixit, David R. Martinez","doi":"10.1126/sciimmunol.aed4909","DOIUrl":"10.1126/sciimmunol.aed4909","url":null,"abstract":"<div >Repeated dengue infections elicit broadly neutralizing antibodies that are protective against severe disease.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 113","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145456911","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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