Pub Date : 2026-01-16DOI: 10.1038/s41577-026-01271-9
Alexandra Flemming
{"title":"Segmented filamentous bacteria in the gut protect against secondary bacterial infections in the lung.","authors":"Alexandra Flemming","doi":"10.1038/s41577-026-01271-9","DOIUrl":"https://doi.org/10.1038/s41577-026-01271-9","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"4 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986526","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 : 2026-01-15DOI: 10.1038/s41577-025-01254-2
Martin Turner,Georg Petkau
Infection triggers one of the most dramatic systemic responses in the body, and the coordinated activation and function of immune cells requires a dynamic regulation of transcriptomes and proteomes. This is achieved by RNA-binding proteins, which, together with RNA, form ribonucleoproteins. These proteins expand the information content of the genome and determine the lifespan, localization and function of RNA. Moreover, they control when, where and how much protein is produced. They can also mediate cell-autonomous immunity to foreign RNA and to misfolded self-RNAs and ensure the fidelity of the transcriptome by acting as RNA modifiers and chaperones to prevent RNA misfolding. These activities are integrated with gene expression programmes that are induced by the pathogen-sensing mechanisms of immune cells, which together activate, and later resolve, immune responses. Here, we review the activities of RNA-binding proteins in immune cells and discuss how perturbations of their function can result in immunodeficiency, autoimmunity and chronic inflammation.
{"title":"RNA-binding proteins and ribonucleoproteins as determinants of immunity.","authors":"Martin Turner,Georg Petkau","doi":"10.1038/s41577-025-01254-2","DOIUrl":"https://doi.org/10.1038/s41577-025-01254-2","url":null,"abstract":"Infection triggers one of the most dramatic systemic responses in the body, and the coordinated activation and function of immune cells requires a dynamic regulation of transcriptomes and proteomes. This is achieved by RNA-binding proteins, which, together with RNA, form ribonucleoproteins. These proteins expand the information content of the genome and determine the lifespan, localization and function of RNA. Moreover, they control when, where and how much protein is produced. They can also mediate cell-autonomous immunity to foreign RNA and to misfolded self-RNAs and ensure the fidelity of the transcriptome by acting as RNA modifiers and chaperones to prevent RNA misfolding. These activities are integrated with gene expression programmes that are induced by the pathogen-sensing mechanisms of immune cells, which together activate, and later resolve, immune responses. Here, we review the activities of RNA-binding proteins in immune cells and discuss how perturbations of their function can result in immunodeficiency, autoimmunity and chronic inflammation.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"20 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986529","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 : 2026-01-12DOI: 10.1038/s41577-025-01258-y
Youxiang Mao,Wenjun Xia,Peng Jiang
Alterations in key metabolic pathways are required for tumour development and the adaptation of tumour cells to intrinsic or extrinsic stresses, as well as for the regulation of immune cell fate and immune responses in the tumour microenvironment. In particular, the dysregulation or alteration of certain metabolites produced by tumour cells has been shown to be important in creating the immunosuppressive tumour microenvironment. Recent studies have broadened our understanding of the interactions between metabolites and antitumour immunity. Here we highlight how, beyond their metabolic role, metabolites can function as signalling molecules to modulate the behaviours of immune cells and tumour cells. We also discuss potential therapeutic strategies targeting specific metabolites and future research directions in metabolite sensing.
{"title":"Metabolites as signalling molecules in the tumour immune microenvironment.","authors":"Youxiang Mao,Wenjun Xia,Peng Jiang","doi":"10.1038/s41577-025-01258-y","DOIUrl":"https://doi.org/10.1038/s41577-025-01258-y","url":null,"abstract":"Alterations in key metabolic pathways are required for tumour development and the adaptation of tumour cells to intrinsic or extrinsic stresses, as well as for the regulation of immune cell fate and immune responses in the tumour microenvironment. In particular, the dysregulation or alteration of certain metabolites produced by tumour cells has been shown to be important in creating the immunosuppressive tumour microenvironment. Recent studies have broadened our understanding of the interactions between metabolites and antitumour immunity. Here we highlight how, beyond their metabolic role, metabolites can function as signalling molecules to modulate the behaviours of immune cells and tumour cells. We also discuss potential therapeutic strategies targeting specific metabolites and future research directions in metabolite sensing.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"248 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955488","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 : 2026-01-09DOI: 10.1038/s41577-026-01264-8
Emery Hoos,Malcolm J W Sim
{"title":"T cell competition in multi-neoantigen cancer vaccines.","authors":"Emery Hoos,Malcolm J W Sim","doi":"10.1038/s41577-026-01264-8","DOIUrl":"https://doi.org/10.1038/s41577-026-01264-8","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"49 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937783","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 : 2026-01-09DOI: 10.1038/s41577-025-01255-1
Lukas Rindlisbacher,Maria N Navarro,Burkhard Becher
Within the IL-12 superfamily of heterodimeric cytokines, IL-12 and IL-23, which share a subunit, are among the most pro-inflammatory members. Both are primarily produced by phagocytes and have key roles in activating and regulating T lymphocytes, natural killer cells and innate lymphoid cells. IL-12 predominantly promotes type 1 immune responses, whereas IL-23 is closely associated with type 3 immunity. Their receptors are also heterodimeric and, upon engagement, they trigger 'cytokine polarization' (the imprinting of functional identities on immune cells by activating lineage-defining transcription factors), which contributes to inflammation and immunopathology. IL-12 has a key role in various inflammatory conditions and is a potent driver of antitumour immunity, and IL-12 delivery is being explored in several clinical trials in cancer. By contrast, IL-23 is essential for maintaining barrier tissue integrity, yet its dysregulation is a central driver of autoimmune diseases such as psoriasis. Beyond their well-established pro-inflammatory roles, studies of both cytokines have also yielded paradoxical findings. Emerging evidence suggests that both IL-12 and IL-23 can also attenuate immune responses. In this Review, we explore the discovery of IL-12 and IL-23, their canonical pro-inflammatory functions, and recent insights into their immunoregulatory roles in inflammation, cancer and autoimmunity.
{"title":"Inflame and restrain - the paradoxical roles of IL-12 and IL-23 in immunity.","authors":"Lukas Rindlisbacher,Maria N Navarro,Burkhard Becher","doi":"10.1038/s41577-025-01255-1","DOIUrl":"https://doi.org/10.1038/s41577-025-01255-1","url":null,"abstract":"Within the IL-12 superfamily of heterodimeric cytokines, IL-12 and IL-23, which share a subunit, are among the most pro-inflammatory members. Both are primarily produced by phagocytes and have key roles in activating and regulating T lymphocytes, natural killer cells and innate lymphoid cells. IL-12 predominantly promotes type 1 immune responses, whereas IL-23 is closely associated with type 3 immunity. Their receptors are also heterodimeric and, upon engagement, they trigger 'cytokine polarization' (the imprinting of functional identities on immune cells by activating lineage-defining transcription factors), which contributes to inflammation and immunopathology. IL-12 has a key role in various inflammatory conditions and is a potent driver of antitumour immunity, and IL-12 delivery is being explored in several clinical trials in cancer. By contrast, IL-23 is essential for maintaining barrier tissue integrity, yet its dysregulation is a central driver of autoimmune diseases such as psoriasis. Beyond their well-established pro-inflammatory roles, studies of both cytokines have also yielded paradoxical findings. Emerging evidence suggests that both IL-12 and IL-23 can also attenuate immune responses. In this Review, we explore the discovery of IL-12 and IL-23, their canonical pro-inflammatory functions, and recent insights into their immunoregulatory roles in inflammation, cancer and autoimmunity.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"20 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937782","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 : 2026-01-07DOI: 10.1038/s41577-025-01248-0
Lydia Sorokin
{"title":"Biochemical signals from the extracellular matrix in inflammation and tumour immunology","authors":"Lydia Sorokin","doi":"10.1038/s41577-025-01248-0","DOIUrl":"https://doi.org/10.1038/s41577-025-01248-0","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"53 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907944","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}