Pub Date : 2025-06-25DOI: 10.1038/s41577-025-01202-0
Boyan K. Tsankov, Dana J. Philpott
A preprint by Srivastava et al. reports that C19S modification of insulin, which occurs in response to a stressed microenvironment, promotes pro-inflammatory T cell activation and memory responses.
{"title":"Insulin neoantigen elicits memory T cell activation in diabetes","authors":"Boyan K. Tsankov, Dana J. Philpott","doi":"10.1038/s41577-025-01202-0","DOIUrl":"10.1038/s41577-025-01202-0","url":null,"abstract":"A preprint by Srivastava et al. reports that C19S modification of insulin, which occurs in response to a stressed microenvironment, promotes pro-inflammatory T cell activation and memory responses.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 8","pages":"557-557"},"PeriodicalIF":60.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478992","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 : 2025-06-24DOI: 10.1038/s41577-025-01201-1
Kirsty Minton
White et al. show that microbiota-specific T cells are licensed by gut inflammation to infiltrate the central nervous system, where cross-reactivity with self-antigens leads to neuropathology.
{"title":"Gut microbiota-specific T cells induce neuroinflammation through molecular mimicry","authors":"Kirsty Minton","doi":"10.1038/s41577-025-01201-1","DOIUrl":"10.1038/s41577-025-01201-1","url":null,"abstract":"White et al. show that microbiota-specific T cells are licensed by gut inflammation to infiltrate the central nervous system, where cross-reactivity with self-antigens leads to neuropathology.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 8","pages":"555-555"},"PeriodicalIF":60.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370466","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 : 2025-06-18DOI: 10.1038/s41577-025-01191-0
Yael Alippe, Joshua Hatterschide, Carolyn B. Coyne, Michael S. Diamond
During pregnancy, the maternal immune system must navigate a balance between fetal tolerance and a response to acquired microbial infections. Cells at the maternal–fetal interface coordinate this response throughout gestational stages in a dynamic manner, integrating endocrine, developmental, inflammatory and metabolic cues. Although many maternal and fetal cell types activate innate immune signalling pathways in response to infections, excessive inflammation can disrupt tolerance, affect placental function and impair fetal development, leading to congenital disease and other pregnancy complications. In this Review, we discuss the mechanisms of pathogen recognition in the maternal and fetal compartments of the placenta and the consequences of these responses to pregnancy outcomes. During pregnancy, innate immune mechanisms at the maternal–fetal interface are important for protecting the developing fetus from pathogens. However, excessive immune activation can be harmful to the fetus, and these pathways must be properly regulated. Here, the authors discuss the growing understanding of the unique innate immune pathways that operate in the maternal and fetal compartments of the placenta.
{"title":"Innate immune responses to pathogens at the maternal–fetal interface","authors":"Yael Alippe, Joshua Hatterschide, Carolyn B. Coyne, Michael S. Diamond","doi":"10.1038/s41577-025-01191-0","DOIUrl":"10.1038/s41577-025-01191-0","url":null,"abstract":"During pregnancy, the maternal immune system must navigate a balance between fetal tolerance and a response to acquired microbial infections. Cells at the maternal–fetal interface coordinate this response throughout gestational stages in a dynamic manner, integrating endocrine, developmental, inflammatory and metabolic cues. Although many maternal and fetal cell types activate innate immune signalling pathways in response to infections, excessive inflammation can disrupt tolerance, affect placental function and impair fetal development, leading to congenital disease and other pregnancy complications. In this Review, we discuss the mechanisms of pathogen recognition in the maternal and fetal compartments of the placenta and the consequences of these responses to pregnancy outcomes. During pregnancy, innate immune mechanisms at the maternal–fetal interface are important for protecting the developing fetus from pathogens. However, excessive immune activation can be harmful to the fetus, and these pathways must be properly regulated. Here, the authors discuss the growing understanding of the unique innate immune pathways that operate in the maternal and fetal compartments of the placenta.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 12","pages":"869-884"},"PeriodicalIF":60.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311690","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 : 2025-06-16DOI: 10.1038/s41577-025-01193-y
Joe N. Frost, Hal Drakesmith
Iron is a cofactor for hundreds of enzymes and biochemical processes that support cellular metabolism across the kingdoms of life. Because of this, the host and pathogen compete for iron as a vital resource. Moreover, research has shown that iron acquisition and iron trafficking have substantial effects on the immune system. This is especially important because iron-related disorders — both deficiency and overload — are common worldwide. In this Review, we describe how immune cells acquire and use iron, which branches of the immune system are most affected by iron and how changes in iron availability can affect infectious diseases, autoinflammatory disorders and antitumour immunity. We also discuss key unanswered questions and potential therapeutic opportunities to manipulate immunity by controlling iron trafficking. Iron is crucial for cellular metabolism, but its availability varies greatly within and between individuals and populations. This Review highlights how iron regulates innate and adaptive cellular and humoral responses affecting protection against infections, tumours and autoimmunity.
{"title":"Iron and the immune system","authors":"Joe N. Frost, Hal Drakesmith","doi":"10.1038/s41577-025-01193-y","DOIUrl":"10.1038/s41577-025-01193-y","url":null,"abstract":"Iron is a cofactor for hundreds of enzymes and biochemical processes that support cellular metabolism across the kingdoms of life. Because of this, the host and pathogen compete for iron as a vital resource. Moreover, research has shown that iron acquisition and iron trafficking have substantial effects on the immune system. This is especially important because iron-related disorders — both deficiency and overload — are common worldwide. In this Review, we describe how immune cells acquire and use iron, which branches of the immune system are most affected by iron and how changes in iron availability can affect infectious diseases, autoinflammatory disorders and antitumour immunity. We also discuss key unanswered questions and potential therapeutic opportunities to manipulate immunity by controlling iron trafficking. Iron is crucial for cellular metabolism, but its availability varies greatly within and between individuals and populations. This Review highlights how iron regulates innate and adaptive cellular and humoral responses affecting protection against infections, tumours and autoimmunity.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 12","pages":"885-899"},"PeriodicalIF":60.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304457","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 : 2025-06-13DOI: 10.1038/s41577-025-01192-z
Emma Lefrançais, Denis Hudrisier, Olivier Neyrolles, Samuel M. Behar, Joel D. Ernst
Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), results in more human mortality than any other single pathogen, in part because of the lack of an effective vaccine. Although T cells are essential for immunity to TB, the mechanisms that provide protective immunity are poorly understood. In this Review, we describe current gaps in our knowledge about T cell-mediated immune responses to M. tuberculosis and discuss how recent technologies, including multiphoton intravital microscopy, spatial multiomics and high-resolution in vivo analyses of cell–cell interactions, may be used to gain insights that can inform the design of T cell-targeted TB vaccines. T cells have an essential role in immune responses to Mycobacterium tuberculosis, but the mechanisms by which they may provide protective immunity remain poorly understood. This Review explores the knowns and unknowns of T cell immunity in tuberculosis and how recent technologies may inform the design of T cell-targeted TB vaccines.
{"title":"Finding and filling the knowledge gaps in mechanisms of T cell-mediated TB immunity to inform vaccine design","authors":"Emma Lefrançais, Denis Hudrisier, Olivier Neyrolles, Samuel M. Behar, Joel D. Ernst","doi":"10.1038/s41577-025-01192-z","DOIUrl":"10.1038/s41577-025-01192-z","url":null,"abstract":"Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), results in more human mortality than any other single pathogen, in part because of the lack of an effective vaccine. Although T cells are essential for immunity to TB, the mechanisms that provide protective immunity are poorly understood. In this Review, we describe current gaps in our knowledge about T cell-mediated immune responses to M. tuberculosis and discuss how recent technologies, including multiphoton intravital microscopy, spatial multiomics and high-resolution in vivo analyses of cell–cell interactions, may be used to gain insights that can inform the design of T cell-targeted TB vaccines. T cells have an essential role in immune responses to Mycobacterium tuberculosis, but the mechanisms by which they may provide protective immunity remain poorly understood. This Review explores the knowns and unknowns of T cell immunity in tuberculosis and how recent technologies may inform the design of T cell-targeted TB vaccines.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 11","pages":"798-815"},"PeriodicalIF":60.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278511","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 : 2025-06-12DOI: 10.1038/s41577-025-01198-7
Benjamin R. Schrank, Betty Y. S. Kim
A preprint by Li et al. presents a comprehensive pan-cancer atlas of tumour-specific peptides that markedly expands the known tumour antigen repertoire.
Li等人的预印本提出了肿瘤特异性肽的全面泛癌症图谱，显着扩展了已知的肿瘤抗原库。
{"title":"Uncovering the hidden landscape of tumour antigens","authors":"Benjamin R. Schrank, Betty Y. S. Kim","doi":"10.1038/s41577-025-01198-7","DOIUrl":"10.1038/s41577-025-01198-7","url":null,"abstract":"A preprint by Li et al. presents a comprehensive pan-cancer atlas of tumour-specific peptides that markedly expands the known tumour antigen repertoire.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 7","pages":"482-482"},"PeriodicalIF":60.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268610","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 : 2025-06-12DOI: 10.1038/s41577-025-01197-8
Brian Y. Soong, Miriam Merad
A preprint by Cortez et al. explores how IL-25 produced in response to helminth infection in mice rewires intestinal ILC2s to retain a 'memory' of prior infection.
{"title":"Gut ILC2s remember IL-25","authors":"Brian Y. Soong, Miriam Merad","doi":"10.1038/s41577-025-01197-8","DOIUrl":"10.1038/s41577-025-01197-8","url":null,"abstract":"A preprint by Cortez et al. explores how IL-25 produced in response to helminth infection in mice rewires intestinal ILC2s to retain a 'memory' of prior infection.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 7","pages":"482-482"},"PeriodicalIF":60.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268544","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 : 2025-06-12DOI: 10.1038/s41577-025-01188-9
Lily Keane, Gerard Clarke, John F. Cryan
Microglia, the resident immune cells of the brain, are now recognized as being active participants in the onset and progression of many neurological and neuropsychiatric disorders. As a result, substantial effort has been made in finding ways to target, deplete or modulate the aberrant phenotypes of the microglia that are present in these different disease states, albeit with varied levels of success. The gut microbiota has recently emerged as a master regulator of microglia throughout the lifespan; here, we propose that this microbiota–microglia cross-talk may have major implications for our understanding of neurological disorders and neuropsychiatric diseases. We focus on the latest advances in understanding gut–microglia communication in the context of microglial heterogeneity and microglia-related functions, as well as considering the evidence for effects of these pathways on diseases and disorders of the central nervous system. We also address the challenges, opportunities and clinical implications of this emerging area of research. This Perspective explores how the gut microbiota influences the function and heterogeneity of microglia, highlighting their roles in neurological and neuropsychiatric disorders, and discusses the therapeutic potential, challenges and clinical implications of targeting microbiota–microglia interactions.
{"title":"A role for microglia in mediating the microbiota–gut–brain axis","authors":"Lily Keane, Gerard Clarke, John F. Cryan","doi":"10.1038/s41577-025-01188-9","DOIUrl":"10.1038/s41577-025-01188-9","url":null,"abstract":"Microglia, the resident immune cells of the brain, are now recognized as being active participants in the onset and progression of many neurological and neuropsychiatric disorders. As a result, substantial effort has been made in finding ways to target, deplete or modulate the aberrant phenotypes of the microglia that are present in these different disease states, albeit with varied levels of success. The gut microbiota has recently emerged as a master regulator of microglia throughout the lifespan; here, we propose that this microbiota–microglia cross-talk may have major implications for our understanding of neurological disorders and neuropsychiatric diseases. We focus on the latest advances in understanding gut–microglia communication in the context of microglial heterogeneity and microglia-related functions, as well as considering the evidence for effects of these pathways on diseases and disorders of the central nervous system. We also address the challenges, opportunities and clinical implications of this emerging area of research. This Perspective explores how the gut microbiota influences the function and heterogeneity of microglia, highlighting their roles in neurological and neuropsychiatric disorders, and discusses the therapeutic potential, challenges and clinical implications of targeting microbiota–microglia interactions.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 11","pages":"847-861"},"PeriodicalIF":60.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268611","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 : 2025-06-04DOI: 10.1038/s41577-025-01186-x
Jacques Behmoaras, Kevin Mulder, Florent Ginhoux, Enrico Petretto
Macrophages are active participants of tissue repair and when normal repair processes fail, fibrosis can ensue, which leads to major organ dysfunction and affects nearly a billion people worldwide. Here we focus on macrophages in the spatiotemporal control of fibrosis, drawing on our understanding of the roles of these cells in organogenesis, adult organ homeostasis and wound repair. We describe recent insights from single-cell transcriptomics studies of human and mouse tissues that reveal macrophage heterogeneity in healthy and fibrotic niches, as well as the pathways underlying macrophage–fibroblast cooperation during progression from inflammation to fibrosis. Finally, we propose a model to explain how macrophage activity over time and across different tissues controls tissue fibrosis, we discuss therapeutic initiatives based on regulation of macrophage activity and we recommend future research directions. Macrophages are crucial regulators of fibrosis. Here the authors describe how distinct subsets of monocytes and macrophages cooperate with fibroblasts across tissues to control progression from inflammation to fibrosis.
{"title":"The spatial and temporal activation of macrophages during fibrosis","authors":"Jacques Behmoaras, Kevin Mulder, Florent Ginhoux, Enrico Petretto","doi":"10.1038/s41577-025-01186-x","DOIUrl":"10.1038/s41577-025-01186-x","url":null,"abstract":"Macrophages are active participants of tissue repair and when normal repair processes fail, fibrosis can ensue, which leads to major organ dysfunction and affects nearly a billion people worldwide. Here we focus on macrophages in the spatiotemporal control of fibrosis, drawing on our understanding of the roles of these cells in organogenesis, adult organ homeostasis and wound repair. We describe recent insights from single-cell transcriptomics studies of human and mouse tissues that reveal macrophage heterogeneity in healthy and fibrotic niches, as well as the pathways underlying macrophage–fibroblast cooperation during progression from inflammation to fibrosis. Finally, we propose a model to explain how macrophage activity over time and across different tissues controls tissue fibrosis, we discuss therapeutic initiatives based on regulation of macrophage activity and we recommend future research directions. Macrophages are crucial regulators of fibrosis. Here the authors describe how distinct subsets of monocytes and macrophages cooperate with fibroblasts across tissues to control progression from inflammation to fibrosis.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 11","pages":"816-830"},"PeriodicalIF":60.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211032","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 : 2025-06-02DOI: 10.1038/s41577-025-01194-x
Mahdieh Golzari-Sorkheh, Juan Carlos Zúñiga-Pflücker
A preprint by Ellul et al. reports that maternal immune activation of mice imprints regulatory T cell dysfunction in offspring that drives autism-like behaviours.
{"title":"Fetal Treg cell reprogramming links maternal immunity to neurodevelopment","authors":"Mahdieh Golzari-Sorkheh, Juan Carlos Zúñiga-Pflücker","doi":"10.1038/s41577-025-01194-x","DOIUrl":"10.1038/s41577-025-01194-x","url":null,"abstract":"A preprint by Ellul et al. reports that maternal immune activation of mice imprints regulatory T cell dysfunction in offspring that drives autism-like behaviours.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 7","pages":"481-481"},"PeriodicalIF":60.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192929","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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