Pub Date : 2024-02-12DOI: 10.1038/s41577-024-01002-y
Lucy Bird
Investigation of neutrophil heterogeneity in tumours reveals the irreversible programming of long-lived, pro-angiogenic neutrophils that drive tumour progression.
{"title":"Neutrophils become pro-angiogenic in tumours","authors":"Lucy Bird","doi":"10.1038/s41577-024-01002-y","DOIUrl":"10.1038/s41577-024-01002-y","url":null,"abstract":"Investigation of neutrophil heterogeneity in tumours reveals the irreversible programming of long-lived, pro-angiogenic neutrophils that drive tumour progression.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"157-157"},"PeriodicalIF":67.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139720230","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 : 2024-02-08DOI: 10.1038/s41577-024-00991-0
David R. Fooksman, Zhixin Jing, Rosa Park
Plasma cells are unique immune effectors, capable of producing large amounts of high-affinity antibodies that protect against pathogenic infections. Although most plasma cells have short lifespans, certain conditions or vaccinations can give rise to long-lived plasma cells (LLPCs) that provide individuals with lifelong protection against pathogen exposure. The nature of these LLPCs is poorly understood; however, recent studies have shed new light on the ontogeny, diversity, maturation and survival of these unique cells. Whereas LLPCs had been thought to arise preferentially from germinal centres, novel genetic tools have revealed that they can originate from various stages throughout the humoral response. Furthermore, new single-cell analyses have shown that mouse and human plasma cells are heterogeneous and may undergo further maturation in situ in the bone marrow niche. Finally, plasma cells were previously considered to be sessile cells maintained in fixed survival niches, but new data show that plasma cell subsets can differentially migrate and organize into clusters that may be associated with survival niches. These descriptive findings provide new insights into how cell-intrinsic programmes and extrinsic factors may regulate the longevity of plasma cells in various contexts, which suggest new research avenues for their functional validation. In this Progress article, Fooksman and colleagues review recent advances in the study of long-lived plasma cells, using genetic labelling tools, RNA sequencing and in vivo imaging to characterize the differentiation and survival of this rare cell type in mice and humans.
{"title":"New insights into the ontogeny, diversity, maturation and survival of long-lived plasma cells","authors":"David R. Fooksman, Zhixin Jing, Rosa Park","doi":"10.1038/s41577-024-00991-0","DOIUrl":"10.1038/s41577-024-00991-0","url":null,"abstract":"Plasma cells are unique immune effectors, capable of producing large amounts of high-affinity antibodies that protect against pathogenic infections. Although most plasma cells have short lifespans, certain conditions or vaccinations can give rise to long-lived plasma cells (LLPCs) that provide individuals with lifelong protection against pathogen exposure. The nature of these LLPCs is poorly understood; however, recent studies have shed new light on the ontogeny, diversity, maturation and survival of these unique cells. Whereas LLPCs had been thought to arise preferentially from germinal centres, novel genetic tools have revealed that they can originate from various stages throughout the humoral response. Furthermore, new single-cell analyses have shown that mouse and human plasma cells are heterogeneous and may undergo further maturation in situ in the bone marrow niche. Finally, plasma cells were previously considered to be sessile cells maintained in fixed survival niches, but new data show that plasma cell subsets can differentially migrate and organize into clusters that may be associated with survival niches. These descriptive findings provide new insights into how cell-intrinsic programmes and extrinsic factors may regulate the longevity of plasma cells in various contexts, which suggest new research avenues for their functional validation. In this Progress article, Fooksman and colleagues review recent advances in the study of long-lived plasma cells, using genetic labelling tools, RNA sequencing and in vivo imaging to characterize the differentiation and survival of this rare cell type in mice and humans.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"461-470"},"PeriodicalIF":67.7,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707363","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 : 2024-02-02DOI: 10.1038/s41577-023-00985-4
Kevan C. Herold, Thomas Delong, Ana Luisa Perdigoto, Noah Biru, Todd M. Brusko, Lucy S. K. Walker
Following the seminal discovery of insulin a century ago, treatment of individuals with type 1 diabetes (T1D) has been largely restricted to efforts to monitor and treat metabolic glucose dysregulation. The recent regulatory approval of the first immunotherapy that targets T cells as a means to delay the autoimmune destruction of pancreatic β-cells highlights the critical role of the immune system in disease pathogenesis and tends to pave the way for other immune-targeted interventions for T1D. Improving the efficacy of such interventions across the natural history of the disease will probably require a more detailed understanding of the immunobiology of T1D, as well as technologies to monitor residual β-cell mass and function. Here we provide an overview of the immune mechanisms that underpin the pathogenesis of T1D, with a particular emphasis on T cells. The first immune-targeted drug for type 1 diabetes (T1D), teplizumab, received regulatory approval by the US FDA in 2022. In this Review, Herold, Walker and colleagues examine the immune mechanisms that underpin T1D and provide an overview of immune-targeted strategies for T1D that are currently in development.
自一个世纪前胰岛素的重大发现以来，对1型糖尿病（T1D）患者的治疗主要局限于监测和治疗代谢性葡萄糖失调。最近，首个以 T 细胞为靶点的免疫疗法获得了监管部门的批准，该疗法可延缓胰腺 β 细胞的自身免疫破坏，这凸显了免疫系统在疾病发病机制中的关键作用，并有望为其他以免疫为靶点的 T1D 干预疗法铺平道路。要提高此类干预措施在疾病自然史中的疗效，可能需要更详细地了解 T1D 的免疫生物学，以及监测残余 β 细胞数量和功能的技术。在此，我们概述了支撑 T1D 发病机制的免疫机制，并特别强调了 T 细胞。
{"title":"The immunology of type 1 diabetes","authors":"Kevan C. Herold, Thomas Delong, Ana Luisa Perdigoto, Noah Biru, Todd M. Brusko, Lucy S. K. Walker","doi":"10.1038/s41577-023-00985-4","DOIUrl":"10.1038/s41577-023-00985-4","url":null,"abstract":"Following the seminal discovery of insulin a century ago, treatment of individuals with type 1 diabetes (T1D) has been largely restricted to efforts to monitor and treat metabolic glucose dysregulation. The recent regulatory approval of the first immunotherapy that targets T cells as a means to delay the autoimmune destruction of pancreatic β-cells highlights the critical role of the immune system in disease pathogenesis and tends to pave the way for other immune-targeted interventions for T1D. Improving the efficacy of such interventions across the natural history of the disease will probably require a more detailed understanding of the immunobiology of T1D, as well as technologies to monitor residual β-cell mass and function. Here we provide an overview of the immune mechanisms that underpin the pathogenesis of T1D, with a particular emphasis on T cells. The first immune-targeted drug for type 1 diabetes (T1D), teplizumab, received regulatory approval by the US FDA in 2022. In this Review, Herold, Walker and colleagues examine the immune mechanisms that underpin T1D and provide an overview of immune-targeted strategies for T1D that are currently in development.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"435-451"},"PeriodicalIF":67.7,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139660021","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 : 2024-02-01DOI: 10.1038/s41577-024-01000-0
Kirsty Minton
Glycosylated RNAs on the surface of neutrophils bind P-selectin on endothelial cells to mediate recruitment to sites of inflammation.
中性粒细胞表面的糖基化 RNA 与内皮细胞上的 P-选择素结合，介导中性粒细胞被招募到炎症部位。
{"title":"Neutrophil surface RNAs promote entry to inflamed sites","authors":"Kirsty Minton","doi":"10.1038/s41577-024-01000-0","DOIUrl":"10.1038/s41577-024-01000-0","url":null,"abstract":"Glycosylated RNAs on the surface of neutrophils bind P-selectin on endothelial cells to mediate recruitment to sites of inflammation.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"158-158"},"PeriodicalIF":67.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139655803","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 : 2024-02-01DOI: 10.1038/s41577-024-00999-6
Carmen Fiuza-Luces, Pedro L. Valenzuela, Beatriz G. Gálvez, Manuel Ramírez, Alejandro López-Soto, Richard J. Simpson, Alejandro Lucia
{"title":"Author Correction: The effect of physical exercise on anticancer immunity","authors":"Carmen Fiuza-Luces, Pedro L. Valenzuela, Beatriz G. Gálvez, Manuel Ramírez, Alejandro López-Soto, Richard J. Simpson, Alejandro Lucia","doi":"10.1038/s41577-024-00999-6","DOIUrl":"10.1038/s41577-024-00999-6","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"229-229"},"PeriodicalIF":67.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41577-024-00999-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672280","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 : 2024-01-30DOI: 10.1038/s41577-024-00997-8
Austeja Baleviciute, Lily Keane
A preprint by Kim et al. shows that the brain parenchyma can be seeded with age with clonal haematopoiesis-derived monocytes that drive neuropathology.
Kim 等人的预印本显示，随着年龄的增长，脑实质中会出现克隆性造血单核细胞，从而引发神经病理学。
{"title":"Clonal haematopoiesis-associated, age-related motor deficits caused by monocyte-derived microglia","authors":"Austeja Baleviciute, Lily Keane","doi":"10.1038/s41577-024-00997-8","DOIUrl":"10.1038/s41577-024-00997-8","url":null,"abstract":"A preprint by Kim et al. shows that the brain parenchyma can be seeded with age with clonal haematopoiesis-derived monocytes that drive neuropathology.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"160-160"},"PeriodicalIF":67.7,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577400","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 : 2024-01-25DOI: 10.1038/s41577-023-00982-7
Aurore Fenis, Olivier Demaria, Laurent Gauthier, Eric Vivier, Emilie Narni-Mancinelli
There have been major advances in the immunotherapy of cancer in recent years, including the development of T cell engagers — antibodies engineered to redirect T cells to recognize and kill cancer cells — for the treatment of haematological malignancies. However, the field still faces several challenges to develop agents that are consistently effective in a majority of patients and cancer types, such as optimizing drug dose, overcoming treatment resistance and improving efficacy in solid tumours. A new generation of T cell-targeted molecules was developed to tackle these issues that are potentially more effective and safer. In addition, agents designed to engage the antitumour activities of other immune cells, including natural killer cells and myeloid cells, are showing promise and have the potential to treat a broader range of cancers. Immune cell engagers — antibody-based molecules engineered to direct immune effector cells to recognize and kill cancer cells — represent a rapidly expanding approach in cancer therapy. Here, the authors bring us up to date with the targets, challenges and opportunities for harnessing the anticancer activities of T cells, natural killer cells and myeloid cells with immune cell engagers.
近年来，癌症免疫疗法取得了重大进展，包括开发出治疗血液系统恶性肿瘤的 T 细胞吞噬剂（T 细胞吞噬剂是一种抗体，可引导 T 细胞识别并杀死癌细胞）。然而，要开发出对大多数患者和癌症类型持续有效的药物，该领域仍面临一些挑战，如优化药物剂量、克服耐药性和提高实体瘤的疗效。新一代 T 细胞靶向分子的开发就是为了解决这些问题，它们可能更有效、更安全。此外，旨在调动其他免疫细胞（包括自然杀伤细胞和类髓鞘细胞）抗肿瘤活性的药物也显示出良好的前景，有望治疗更广泛的癌症。
{"title":"New immune cell engagers for cancer immunotherapy","authors":"Aurore Fenis, Olivier Demaria, Laurent Gauthier, Eric Vivier, Emilie Narni-Mancinelli","doi":"10.1038/s41577-023-00982-7","DOIUrl":"10.1038/s41577-023-00982-7","url":null,"abstract":"There have been major advances in the immunotherapy of cancer in recent years, including the development of T cell engagers — antibodies engineered to redirect T cells to recognize and kill cancer cells — for the treatment of haematological malignancies. However, the field still faces several challenges to develop agents that are consistently effective in a majority of patients and cancer types, such as optimizing drug dose, overcoming treatment resistance and improving efficacy in solid tumours. A new generation of T cell-targeted molecules was developed to tackle these issues that are potentially more effective and safer. In addition, agents designed to engage the antitumour activities of other immune cells, including natural killer cells and myeloid cells, are showing promise and have the potential to treat a broader range of cancers. Immune cell engagers — antibody-based molecules engineered to direct immune effector cells to recognize and kill cancer cells — represent a rapidly expanding approach in cancer therapy. Here, the authors bring us up to date with the targets, challenges and opportunities for harnessing the anticancer activities of T cells, natural killer cells and myeloid cells with immune cell engagers.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"471-486"},"PeriodicalIF":67.7,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564499","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 : 2024-01-18DOI: 10.1038/s41577-024-00992-z
Laure F. Pittet, Christie C. A. Noble, Nicole L. Messina, Nigel Curtis
While anticipating the development of a COVID-19-specific vaccine, several randomized controlled trials (RCTs) explored the potential of BCG vaccination to protect against COVID-19, based on trials demonstrating beneficial effects of BCG vaccination on unrelated infections and all-cause mortality in neonates in high-mortality geographical settings. Results are now available from 12 RCTs, which suggest that BCG vaccination is not an effective intervention against COVID-19. That the BCG–COVID-19 trials failed to meet expectation emphasizes the importance of rigorous clinical trials to validate hypotheses, even in urgent situations such as a pandemic.
{"title":"Using BCG vaccination to protect against COVID-19: when reality fails to meet expectation","authors":"Laure F. Pittet, Christie C. A. Noble, Nicole L. Messina, Nigel Curtis","doi":"10.1038/s41577-024-00992-z","DOIUrl":"10.1038/s41577-024-00992-z","url":null,"abstract":"While anticipating the development of a COVID-19-specific vaccine, several randomized controlled trials (RCTs) explored the potential of BCG vaccination to protect against COVID-19, based on trials demonstrating beneficial effects of BCG vaccination on unrelated infections and all-cause mortality in neonates in high-mortality geographical settings. Results are now available from 12 RCTs, which suggest that BCG vaccination is not an effective intervention against COVID-19. That the BCG–COVID-19 trials failed to meet expectation emphasizes the importance of rigorous clinical trials to validate hypotheses, even in urgent situations such as a pandemic.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"83-84"},"PeriodicalIF":67.7,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491028","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 : 2024-01-15DOI: 10.1038/s41577-023-00979-2
Stephen W. Tuffs, Karine Dufresne, Aanchal Rishi, Nicholas R. Walton, John K. McCormick
Bacterial T cell superantigens (SAgs) are a family of microbial exotoxins that function to activate large numbers of T cells simultaneously. SAgs activate T cells by direct binding and crosslinking of the lateral regions of MHC class II molecules on antigen-presenting cells with T cell receptors (TCRs) on T cells; these interactions alter the normal TCR–peptide–MHC class II architecture to activate T cells in a manner that is independent of the antigen specificity of the TCR. SAgs have well-recognized, central roles in human diseases such as toxic shock syndrome and scarlet fever through their quantitative effects on the T cell response; in addition, numerous other consequences of SAg-driven T cell activation are now being recognized, including direct roles in the pathogenesis of endocarditis, bloodstream infections, skin disease and pharyngitis. In this Review, we summarize the expanding family of bacterial SAgs and how these toxins can engage highly diverse adaptive immune receptors. We highlight recent findings regarding how SAg-driven manipulation of the adaptive immune response may operate in multiple human diseases, as well as contributing to the biology and life cycle of SAg-producing bacterial pathogens. This Review provides an updated assessment of the expanding family of T cell-activating bacterial superantigens, emphasizing potential roles of these toxins in various disease states as well as their contribution to the evolution of the bacterial pathogens Staphylococcus aureus and Streptococcus pyogenes.
细菌 T 细胞超抗原（SAgs）是微生物外毒素的一个家族，具有同时激活大量 T 细胞的功能。SAgs 通过抗原递呈细胞上 MHC II 类分子的横向区域与 T 细胞上的 T 细胞受体（TCR）直接结合和交联来激活 T 细胞；这些相互作用改变了正常的 TCR 肽-MHC II 类结构，从而以一种独立于 TCR 抗原特异性的方式激活 T 细胞。通过对 T 细胞反应的定量影响，SAgs 在中毒性休克综合症和猩红热等人类疾病中发挥着公认的核心作用；此外，SAg 驱动的 T 细胞活化还产生了许多其他后果，包括在心内膜炎、血流感染、皮肤病和咽炎的发病机制中发挥直接作用。在这篇综述中，我们总结了不断扩大的细菌 SAg 家族，以及这些毒素如何与高度多样化的适应性免疫受体发生作用。我们重点介绍了最近的研究发现，即由 SAg 驱动的适应性免疫反应是如何在多种人类疾病中发挥作用的，以及对产生 SAg 的细菌病原体的生物学和生命周期的影响。
{"title":"Novel insights into the immune response to bacterial T cell superantigens","authors":"Stephen W. Tuffs, Karine Dufresne, Aanchal Rishi, Nicholas R. Walton, John K. McCormick","doi":"10.1038/s41577-023-00979-2","DOIUrl":"10.1038/s41577-023-00979-2","url":null,"abstract":"Bacterial T cell superantigens (SAgs) are a family of microbial exotoxins that function to activate large numbers of T cells simultaneously. SAgs activate T cells by direct binding and crosslinking of the lateral regions of MHC class II molecules on antigen-presenting cells with T cell receptors (TCRs) on T cells; these interactions alter the normal TCR–peptide–MHC class II architecture to activate T cells in a manner that is independent of the antigen specificity of the TCR. SAgs have well-recognized, central roles in human diseases such as toxic shock syndrome and scarlet fever through their quantitative effects on the T cell response; in addition, numerous other consequences of SAg-driven T cell activation are now being recognized, including direct roles in the pathogenesis of endocarditis, bloodstream infections, skin disease and pharyngitis. In this Review, we summarize the expanding family of bacterial SAgs and how these toxins can engage highly diverse adaptive immune receptors. We highlight recent findings regarding how SAg-driven manipulation of the adaptive immune response may operate in multiple human diseases, as well as contributing to the biology and life cycle of SAg-producing bacterial pathogens. This Review provides an updated assessment of the expanding family of T cell-activating bacterial superantigens, emphasizing potential roles of these toxins in various disease states as well as their contribution to the evolution of the bacterial pathogens Staphylococcus aureus and Streptococcus pyogenes.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"417-434"},"PeriodicalIF":67.7,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139468646","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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