{"title":"Single-cell proteomics sheds light on neutrophil diversity in glioblastoma","authors":"Aglaia Skolariki, Eileen E. Parkes","doi":"10.1038/s41577-025-01241-7","DOIUrl":"10.1038/s41577-025-01241-7","url":null,"abstract":"A preprint by Sadiku et al. characterizes neutrophil diversity in glioblastoma using a new workflow for single-cell proteomic profiling.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 12","pages":"866-866"},"PeriodicalIF":60.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484912","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 : 2025-11-11DOI: 10.1038/s41577-025-01240-8
Shelley Herbrich, Padmanee Sharma
A preprint by Srinivasan et al. describes the role of the gut microbiota and serum amyloid A in regulating retinoid flux that is important for myeloid cell migration and T cell priming.
{"title":"Microbiota and vitamin A flux shape intestinal T cells","authors":"Shelley Herbrich, Padmanee Sharma","doi":"10.1038/s41577-025-01240-8","DOIUrl":"10.1038/s41577-025-01240-8","url":null,"abstract":"A preprint by Srinivasan et al. describes the role of the gut microbiota and serum amyloid A in regulating retinoid flux that is important for myeloid cell migration and T cell priming.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 12","pages":"866-866"},"PeriodicalIF":60.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484913","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 : 2025-11-11DOI: 10.1038/s41577-025-01243-5
Laura Rosenberg, Nicolas Vabret
A preprint by Rivera et al. explores how retroelement expression establishes a tolerogenic environment towards food antigens in the gut, shedding new insights into the immune regulatory role of retroelements.
{"title":"Retroelements orchestrate gut tolerance","authors":"Laura Rosenberg, Nicolas Vabret","doi":"10.1038/s41577-025-01243-5","DOIUrl":"10.1038/s41577-025-01243-5","url":null,"abstract":"A preprint by Rivera et al. explores how retroelement expression establishes a tolerogenic environment towards food antigens in the gut, shedding new insights into the immune regulatory role of retroelements.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 12","pages":"867-867"},"PeriodicalIF":60.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492639","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 : 2025-11-06DOI: 10.1038/s41577-025-01242-6
Lucy Bird
Lipid transport regulates activation of intestinal T helper 17 cells and thereby limits dietary fat absorption and diet-induced weight gain.
脂质转运调节肠道辅助性T 17细胞的激活，从而限制膳食脂肪吸收和饮食引起的体重增加。
{"title":"How T cells handle lipids","authors":"Lucy Bird","doi":"10.1038/s41577-025-01242-6","DOIUrl":"10.1038/s41577-025-01242-6","url":null,"abstract":"Lipid transport regulates activation of intestinal T helper 17 cells and thereby limits dietary fat absorption and diet-induced weight gain.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 12","pages":"863-863"},"PeriodicalIF":60.9,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447259","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 : 2025-11-05DOI: 10.1038/s41577-025-01244-4
Kirsty Minton
Sanchez-Garcia et al. report that systemic hypoxia-induced epigenetic reprogramming of neutrophil progenitors in the bone marrow reduces their effector function to limit lung tissue damage.
{"title":"Hypoxia-induced epigenetic reprogramming of neutrophil progenitors","authors":"Kirsty Minton","doi":"10.1038/s41577-025-01244-4","DOIUrl":"10.1038/s41577-025-01244-4","url":null,"abstract":"Sanchez-Garcia et al. report that systemic hypoxia-induced epigenetic reprogramming of neutrophil progenitors in the bone marrow reduces their effector function to limit lung tissue damage.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 12","pages":"864-864"},"PeriodicalIF":60.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440940","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 : 2025-10-31DOI: 10.1038/s41577-025-01231-9
Kai Li,David M Underhill
The process of phagocytosis creates intracellular compartments (organelles known as phagosomes) that are central hubs for innate immune sensing of potentially dangerous microorganisms, cells, cellular debris and foreign objects. Receptors, enzymes and signalling molecules are specifically enriched in these compartments, wherein they learn everything they can about the phagocytosed material and signal for the cell to mount appropriate responses. The phagosome organelle is also a compartment that facilitates nutrient and metabolite harvesting from internalized materials. This Review explores recent developments in our understanding of phagocytosis as a specific mechanism of innate immune sensing. We discuss efforts to identify the catalogue of proteins that are enriched in different types of phagosomes to learn how these molecules work together to tailor inflammatory and antimicrobial immune responses.
{"title":"Phagocytosis: a process that shapes immune responses to engulfed meals.","authors":"Kai Li,David M Underhill","doi":"10.1038/s41577-025-01231-9","DOIUrl":"https://doi.org/10.1038/s41577-025-01231-9","url":null,"abstract":"The process of phagocytosis creates intracellular compartments (organelles known as phagosomes) that are central hubs for innate immune sensing of potentially dangerous microorganisms, cells, cellular debris and foreign objects. Receptors, enzymes and signalling molecules are specifically enriched in these compartments, wherein they learn everything they can about the phagocytosed material and signal for the cell to mount appropriate responses. The phagosome organelle is also a compartment that facilitates nutrient and metabolite harvesting from internalized materials. This Review explores recent developments in our understanding of phagocytosis as a specific mechanism of innate immune sensing. We discuss efforts to identify the catalogue of proteins that are enriched in different types of phagosomes to learn how these molecules work together to tailor inflammatory and antimicrobial immune responses.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"1 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411635","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 concept of structural immunity, as defined in this Perspective, posits that the first line of immune defence against foreign agents and tissue damage involves the preventative, physical reinforcement of tissue barriers and that this fundamental task can be directly or indirectly regulated by immune cells. Indeed, several types of leukocytes can help build protective barriers when required, potentially either by depositing matrix components themselves in certain circumstances or, more generally, by interactions with canonical structural cells and the existing extracellular matrix. This concept of structural functions of immune cells challenges the rigidity with which mammalian tissue organization and immune defence have been traditionally compartmentalized. Although there is strong momentum in the evidence for structural immunity that has been acquired so far, the field lacks a comprehensive overview of these data as well as a critical evaluation of this concept. Here, we place independent findings from several groups into a working model of immune cells as the architects of tissue barriers, to present a framework on which new concepts and findings in this area can develop.
{"title":"Structural immunity: immune cells as architects of tissue barriers.","authors":"Alaz Ozcan,Tommaso Vicanolo,Veronique Angeli,Yuval Rinkevich,Andrés Hidalgo","doi":"10.1038/s41577-025-01230-w","DOIUrl":"https://doi.org/10.1038/s41577-025-01230-w","url":null,"abstract":"The concept of structural immunity, as defined in this Perspective, posits that the first line of immune defence against foreign agents and tissue damage involves the preventative, physical reinforcement of tissue barriers and that this fundamental task can be directly or indirectly regulated by immune cells. Indeed, several types of leukocytes can help build protective barriers when required, potentially either by depositing matrix components themselves in certain circumstances or, more generally, by interactions with canonical structural cells and the existing extracellular matrix. This concept of structural functions of immune cells challenges the rigidity with which mammalian tissue organization and immune defence have been traditionally compartmentalized. Although there is strong momentum in the evidence for structural immunity that has been acquired so far, the field lacks a comprehensive overview of these data as well as a critical evaluation of this concept. Here, we place independent findings from several groups into a working model of immune cells as the architects of tissue barriers, to present a framework on which new concepts and findings in this area can develop.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"13 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381010","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 : 2025-10-16DOI: 10.1038/s41577-025-01226-6
Daniel A Winer,Huixun Du,JangKeun Kim,Veronica Chang,Marissa Burke,Shawn Winer,Sylvain V Costes,Jean-Pol Frippiat,Clarence Sams,Amber M Paul,Honglu Wu,Oliver Ullrich,Sarah Baatout,Afshin Beheshti,Christopher E Mason,Alexander Choukér,Brian E Crucian
As humans embark on longer and deeper missions into space, it is crucial to understand how spaceflight impacts the immune system. Decades of discoveries, bolstered by recent multiomic analyses, have identified key immune processes that are affected by the spaceflight environment. These findings form the foundations of the emerging field of 'astroimmunology'. Spaceflight stressors - such as microgravity and galactic cosmic radiation - and other mission-associated variables, including psychological stress and abnormal circadian rhythms, can disrupt or adversely affect immune cell biology. In addition, spaceflight alters host-microbiome interactions, which can increase susceptibility to opportunistic pathogens and viral reactivation. Although ground-based analogues for human spaceflight have provided insights into these stressors individually, their combined effects during spaceflight remain less understood. This Review explores our current knowledge of the effects of spaceflight stressors on the immune system and the clinical implications for human space exploration. It also highlights current and developing countermeasures, including machine-learning approaches, advanced monitoring technologies and standardized biobanking, that can facilitate research into the impact of spaceflight on the immune system. Looking ahead, progressing from low Earth orbit missions to long-term missions to the Moon, Mars and beyond will introduce new challenges, including increased radiation, variable gravity and regolith exposure. We discuss these prospective challenges and outline potential preventive and mitigative strategies for sustaining immune health to enable safe and effective space exploration and habitation of distant worlds.
{"title":"Astroimmunology: the effects of spaceflight and its associated stressors on the immune system.","authors":"Daniel A Winer,Huixun Du,JangKeun Kim,Veronica Chang,Marissa Burke,Shawn Winer,Sylvain V Costes,Jean-Pol Frippiat,Clarence Sams,Amber M Paul,Honglu Wu,Oliver Ullrich,Sarah Baatout,Afshin Beheshti,Christopher E Mason,Alexander Choukér,Brian E Crucian","doi":"10.1038/s41577-025-01226-6","DOIUrl":"https://doi.org/10.1038/s41577-025-01226-6","url":null,"abstract":"As humans embark on longer and deeper missions into space, it is crucial to understand how spaceflight impacts the immune system. Decades of discoveries, bolstered by recent multiomic analyses, have identified key immune processes that are affected by the spaceflight environment. These findings form the foundations of the emerging field of 'astroimmunology'. Spaceflight stressors - such as microgravity and galactic cosmic radiation - and other mission-associated variables, including psychological stress and abnormal circadian rhythms, can disrupt or adversely affect immune cell biology. In addition, spaceflight alters host-microbiome interactions, which can increase susceptibility to opportunistic pathogens and viral reactivation. Although ground-based analogues for human spaceflight have provided insights into these stressors individually, their combined effects during spaceflight remain less understood. This Review explores our current knowledge of the effects of spaceflight stressors on the immune system and the clinical implications for human space exploration. It also highlights current and developing countermeasures, including machine-learning approaches, advanced monitoring technologies and standardized biobanking, that can facilitate research into the impact of spaceflight on the immune system. Looking ahead, progressing from low Earth orbit missions to long-term missions to the Moon, Mars and beyond will introduce new challenges, including increased radiation, variable gravity and regolith exposure. We discuss these prospective challenges and outline potential preventive and mitigative strategies for sustaining immune health to enable safe and effective space exploration and habitation of distant worlds.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"13 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305720","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 : 2025-10-14DOI: 10.1038/s41577-025-01229-3
Zachary L Lamplugh,Nils Wellhausen,Carl H June,Yi Fan
Chimeric antigen receptor (CAR) T cell therapy holds significant promise for the treatment of cancer; however, its efficacy in solid tumours is substantially hindered by the immunosuppressive tumour microenvironment (TME). Solid tumours can resist immunotherapy by impairing T cell trafficking, function and persistence. One of the initial obstacles that CAR T cells encounter is the abnormal tumour vasculature, which restricts efficient T cell infiltration, further compounded by a dense extracellular matrix. CAR T cells that do infiltrate the tumours are outnumbered by immunosuppressive cells such as regulatory T cells, myeloid-derived suppressor cells and tumour-associated macrophages. Additionally, tumour cells can contribute to CAR T cell resistance by upregulating immune checkpoint molecules, such as PDL1 and CTLA4, and engage in metabolic competition. In this Review, we discuss how cellular and non-cellular components of the TME impair CAR T cell therapy and consider potential strategies to improve CAR T cell therapies for solid tumours, either by reprogramming the TME or by engineering CAR T cells to resist the immunosuppressive effects of the TME.
{"title":"Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.","authors":"Zachary L Lamplugh,Nils Wellhausen,Carl H June,Yi Fan","doi":"10.1038/s41577-025-01229-3","DOIUrl":"https://doi.org/10.1038/s41577-025-01229-3","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy holds significant promise for the treatment of cancer; however, its efficacy in solid tumours is substantially hindered by the immunosuppressive tumour microenvironment (TME). Solid tumours can resist immunotherapy by impairing T cell trafficking, function and persistence. One of the initial obstacles that CAR T cells encounter is the abnormal tumour vasculature, which restricts efficient T cell infiltration, further compounded by a dense extracellular matrix. CAR T cells that do infiltrate the tumours are outnumbered by immunosuppressive cells such as regulatory T cells, myeloid-derived suppressor cells and tumour-associated macrophages. Additionally, tumour cells can contribute to CAR T cell resistance by upregulating immune checkpoint molecules, such as PDL1 and CTLA4, and engage in metabolic competition. In this Review, we discuss how cellular and non-cellular components of the TME impair CAR T cell therapy and consider potential strategies to improve CAR T cell therapies for solid tumours, either by reprogramming the TME or by engineering CAR T cells to resist the immunosuppressive effects of the TME.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"54 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288399","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 : 2025-10-09DOI: 10.1038/s41577-025-01223-9
Jeremy G Baldwin,Christoph Heuser-Loy,Luca Gattinoni
Organelles are the internal batteries, gears, actuators, 3D printers and transmitters that drive cell function. Their composition and activity vary between cell types depending on functional demands. In T cells, which are key mediators of immunosurveillance and tumour eradication, organelles are relatively few and function at basal levels when cells are at rest. However, upon activation, they increase in number and size and undergo extensive remodelling to support rapid proliferation, effector differentiation and adaptation to diverse microenvironments, including the tumour microenvironment, thereby enabling efficient clearance of target cells. In this Review, we provide an overview of recent advances in our understanding of how various organelles contribute to T cell-mediated antitumour immunity. We also discuss emerging strategies to modulate organelle functions - from organelle-targeted therapies and their use as cargo delivery systems to the transfer or transplantation of native or synthetic organelles - that have the potential to enhance cancer immunotherapies involving immune-checkpoint blockade or the adoptive transfer of T cells.
{"title":"Targeting organelle function in T cells for cancer immunotherapy.","authors":"Jeremy G Baldwin,Christoph Heuser-Loy,Luca Gattinoni","doi":"10.1038/s41577-025-01223-9","DOIUrl":"https://doi.org/10.1038/s41577-025-01223-9","url":null,"abstract":"Organelles are the internal batteries, gears, actuators, 3D printers and transmitters that drive cell function. Their composition and activity vary between cell types depending on functional demands. In T cells, which are key mediators of immunosurveillance and tumour eradication, organelles are relatively few and function at basal levels when cells are at rest. However, upon activation, they increase in number and size and undergo extensive remodelling to support rapid proliferation, effector differentiation and adaptation to diverse microenvironments, including the tumour microenvironment, thereby enabling efficient clearance of target cells. In this Review, we provide an overview of recent advances in our understanding of how various organelles contribute to T cell-mediated antitumour immunity. We also discuss emerging strategies to modulate organelle functions - from organelle-targeted therapies and their use as cargo delivery systems to the transfer or transplantation of native or synthetic organelles - that have the potential to enhance cancer immunotherapies involving immune-checkpoint blockade or the adoptive transfer of T cells.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"18 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254762","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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