{"title":"Iron and the immune system","authors":"Joe N. Frost, Hal Drakesmith","doi":"10.1038/s41577-025-01193-y","DOIUrl":"https://doi.org/10.1038/s41577-025-01193-y","url":null,"abstract":"<p>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.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"14 1","pages":""},"PeriodicalIF":100.3,"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}
Emma Lefrançais, Denis Hudrisier, Olivier Neyrolles, Samuel M. Behar, Joel D. Ernst
{"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":"https://doi.org/10.1038/s41577-025-01192-z","url":null,"abstract":"<p><i>Mycobacterium tuberculosis</i>, 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 <i>M. tuberculosis</i> 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.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"10 1","pages":""},"PeriodicalIF":100.3,"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}
{"title":"Uncovering the hidden landscape of tumour antigens","authors":"Benjamin R. Schrank, Betty Y. S. Kim","doi":"10.1038/s41577-025-01198-7","DOIUrl":"https://doi.org/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":"44 1","pages":""},"PeriodicalIF":100.3,"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}
{"title":"Gut ILC2s remember IL-25","authors":"Brian Y. Soong, Miriam Merad","doi":"10.1038/s41577-025-01197-8","DOIUrl":"https://doi.org/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":"5 1","pages":""},"PeriodicalIF":100.3,"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}
{"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":"https://doi.org/10.1038/s41577-025-01188-9","url":null,"abstract":"<p>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.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"47 1","pages":""},"PeriodicalIF":100.3,"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}
Jacques Behmoaras, Kevin Mulder, Florent Ginhoux, Enrico Petretto
{"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":"https://doi.org/10.1038/s41577-025-01186-x","url":null,"abstract":"<p>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.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"9 1","pages":""},"PeriodicalIF":100.3,"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}
Mahdieh Golzari-Sorkheh, Juan Carlos Zúñiga-Pflücker
{"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":"https://doi.org/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 offsping that drives autism-like behaviours.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"50 1","pages":""},"PeriodicalIF":100.3,"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}
{"title":"Granzyme B from maternal NK cells perturbs fetal brain development","authors":"Lucy Bird","doi":"10.1038/s41577-025-01196-9","DOIUrl":"https://doi.org/10.1038/s41577-025-01196-9","url":null,"abstract":"A study describes how maternal immune activation can lead to neurodevelopmental deficits in offspring, through a mechanism involving granzyme B release by decidual natural killer cells.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"68 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176660","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}
Aki Sinkkonen, Marja Roslund, Chrysanthi Skevaki, Blandina T. Mmbaga, Kari C. Nadeau, Harald Renz
{"title":"Can we improve immune health by restoring microbial biodiversity?","authors":"Aki Sinkkonen, Marja Roslund, Chrysanthi Skevaki, Blandina T. Mmbaga, Kari C. Nadeau, Harald Renz","doi":"10.1038/s41577-025-01190-1","DOIUrl":"https://doi.org/10.1038/s41577-025-01190-1","url":null,"abstract":"Diverse microbial exposures in early life reduce the risk of inflammatory conditions, including allergies and autoimmunity. Emerging data suggest that microbial diversity is as important as microbial exposures for shaping the immune system. Here we highlight recent clinical trials that have attempted to restore immune regulation by increasing microbial biodiversity.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"132 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145517","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}