Nature Reviews Immunology最新文献_第10页

Adipokines: masterminds of metabolic inflammation 脂肪因子：代谢炎症的主谋

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-11-07 DOI: 10.1038/s41577-024-01103-8

Herbert Tilg, Gianluca Ianiro, Antonio Gasbarrini, Timon E. Adolph

{"title":"Adipokines: masterminds of metabolic inflammation","authors":"Herbert Tilg, Gianluca Ianiro, Antonio Gasbarrini, Timon E. Adolph","doi":"10.1038/s41577-024-01103-8","DOIUrl":"10.1038/s41577-024-01103-8","url":null,"abstract":"Adipose tissue is an immunologically active organ that controls host physiology, partly through the release of mediators termed adipokines. In obesity, adipocytes and infiltrating leukocytes produce adipokines, which include the hormones adiponectin and leptin and cytokines such as tumour necrosis factor and IL-1β. These adipokines orchestrate immune responses that are collectively referred to as metabolic inflammation. Consequently, metabolic inflammation characterizes metabolic disorders and promotes distinct disease aspects, such as insulin resistance, metabolic dysfunction-associated liver disease and cardiovascular complications. In this unifying concept, adipokines participate in the immunological cross-talk that occurs between metabolically active organs in metabolic diseases, highlighting the fundamental role of adipokines in obesity and their potential for therapeutic intervention. Here, we summarize how adipokines shape metabolic inflammation in mice and humans, focusing on their contribution to metabolic disorders in the setting of obesity and discussing their value as therapeutic targets. This Review discusses how adipose tissue can regulate host immune function via the release of adipokines, including adiponectin, leptin and various cytokines. These adipokines contribute to immune responses and metabolic inflammation and can have both beneficial and detrimental effects on host physiology. In obesity, adipokine release can promote insulin resistance and cardiovascular diseases; as such, there is interest in targeting these mediators for therapy of various metabolic disorders.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"250-265"},"PeriodicalIF":67.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594375","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}

引用次数: 0

Decoding the human prenatal immune system with single-cell multi-omics 用单细胞多组学解码人类产前免疫系统

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-31 DOI: 10.1038/s41577-024-01099-1

Muzlifah Haniffa, Aidan Maartens, Elena Winheim, Laura Jardine

{"title":"Decoding the human prenatal immune system with single-cell multi-omics","authors":"Muzlifah Haniffa, Aidan Maartens, Elena Winheim, Laura Jardine","doi":"10.1038/s41577-024-01099-1","DOIUrl":"10.1038/s41577-024-01099-1","url":null,"abstract":"The human immune system is made up of a huge variety of cell types each with unique functions. Local networks of resident immune cells are poised to sense and protect against pathogen entry, whereas more widespread innate and adaptive immune networks provide first rapid, then long-lasting and targeted responses. However, how we develop such a diverse and complex system remains unknown. Studying human development directly has been challenging in the past, but recent advances in single-cell and spatial genomics, together with the co-ordinated efforts of the Human Cell Atlas and other initiatives, have led to new studies that map the development of the human immune system in unprecedented detail. In this Review, we consider the timings, transitions, cell types and tissue microenvironments that are crucial for building the human immune system. We also compare and contrast the human system with model species and in vitro systems, and discuss how an understanding of prenatal immune system development will improve our knowledge of human disease. Single-cell multi-omic profiling has revealed how the immune system is established in the human embryo, mapping in unprecedented detail the emergence of progenitors, the handover of haematopoiesis between sites and the diversification of cell lineages across the body.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"285-297"},"PeriodicalIF":67.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556341","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}

引用次数: 0

Insights into immune cell–fibroblast communication in heart disease 透视心脏病中免疫细胞与成纤维细胞的交流

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-30 DOI: 10.1038/s41577-024-01109-2

Alexandra Flemming

引用次数: 0

Targeting ER stress sensor restores immunogenicity of chemotherapy 靶向ER应激传感器可恢复化疗的免疫原性

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-28 DOI: 10.1038/s41577-024-01107-4

Yvonne Bordon

引用次数: 0

Obesity-associated intratumoral acidity promotes pro-tumorigenic macrophages 与肥胖有关的瘤内酸性促进了促肿瘤生成的巨噬细胞

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-28 DOI: 10.1038/s41577-024-01110-9

Kirsty Minton

引用次数: 0

Human macrophages in pancreas and skin shape prenatal organogenesis 胰腺和皮肤中的人类巨噬细胞塑造了产前器官形成过程

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-22 DOI: 10.1038/s41577-024-01106-5

Kirsty Minton

引用次数: 0

From TCR fundamental research to innovative chimeric antigen receptor design 从 TCR 基础研究到创新型嵌合抗原受体设计

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-21 DOI: 10.1038/s41577-024-01093-7

Susana Minguet, Marcela V. Maus, Wolfgang W. Schamel

{"title":"From TCR fundamental research to innovative chimeric antigen receptor design","authors":"Susana Minguet, Marcela V. Maus, Wolfgang W. Schamel","doi":"10.1038/s41577-024-01093-7","DOIUrl":"10.1038/s41577-024-01093-7","url":null,"abstract":"Engineered T cells that express chimeric antigen receptors (CARs) have transformed the treatment of haematological cancers. CARs combine the tumour-antigen-binding function of antibodies with the signalling functions of the T cell receptor (TCR) ζ chain and co-stimulatory receptors. The resulting constructs aim to mimic the TCR-based and co-receptor-based activation of T cells. Although these have been successful for some types of cancer, new CAR formats are needed, to limit side effects and broaden their use to solid cancers. Insights into the mechanisms of TCR signalling, including the identification of signalling motifs that are not present in the TCR ζ chain and mechanistic insights in TCR activation, have enabled the development of CAR formats that outcompete the current CARs in preclinical mouse models and clinical trials. In this Perspective, we explore the mechanistic rationale behind new CAR designs. CAR T cells have transformed the treatment of some haematological cancers. This Perspective explores how insights into T cell receptor signalling have enabled the engineering of CAR formats that can outcompete currently approved CARs in preclinical models and clinical trials.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"212-224"},"PeriodicalIF":67.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452629","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}

引用次数: 0

Vax-Innate: improving therapeutic cancer vaccines by modulating T cells and the tumour microenvironment Vax-Innate：通过调节 T 细胞和肿瘤微环境改进治疗性癌症疫苗

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-21 DOI: 10.1038/s41577-024-01091-9

Faezzah Baharom, Dalton Hermans, Lélia Delamarre, Robert A. Seder

{"title":"Vax-Innate: improving therapeutic cancer vaccines by modulating T cells and the tumour microenvironment","authors":"Faezzah Baharom, Dalton Hermans, Lélia Delamarre, Robert A. Seder","doi":"10.1038/s41577-024-01091-9","DOIUrl":"10.1038/s41577-024-01091-9","url":null,"abstract":"T cells have a critical role in mediating antitumour immunity. The success of immune checkpoint inhibitors (ICIs) for cancer treatment highlights how enhancing endogenous T cell responses can mediate tumour regression. However, mortality remains high for many cancers, especially in the metastatic setting. Based on advances in the genetic characterization of tumours and identification of tumour-specific antigens, individualized therapeutic cancer vaccines targeting mutated tumour antigens (neoantigens) are being developed to generate tumour-specific T cells for improved therapeutic responses. Early clinical trials using individualized neoantigen vaccines for patients with advanced disease had limited clinical efficacy despite demonstrated induction of T cell responses. Therefore, enhancing T cell activity by improving the magnitude, quality and breadth of T cell responses following vaccination is one current goal for improving outcome against metastatic tumours. Another major consideration is how T cells can be further optimized to function within the tumour microenvironment (TME). In this Perspective, we focus on neoantigen vaccines and propose a new approach, termed Vax-Innate, in which vaccination through intravenous delivery or in combination with tumour-targeting immune modulators may improve antitumour efficacy by simultaneously increasing the magnitude, quality and breadth of T cells while transforming the TME into a largely immunostimulatory environment for T cells. This Perspective considers present and historical paradigms of therapeutic cancer vaccines and describes a conceptual framework, termed Vax-Innate, to simultaneously generate robust tumour-specific T cell responses and remodel the suppressive tumour microenvironment (TME). The authors detail how this strategy could be achieved through systemic vaccination and by using immune modulators to improve dendritic cell and macrophage function in the TME.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"195-211"},"PeriodicalIF":67.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452630","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}

引用次数: 0

The roles of arginases and arginine in immunity 精氨酸酶和精氨酸在免疫中的作用

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-17 DOI: 10.1038/s41577-024-01098-2

Stefania Canè, Roger Geiger, Vincenzo Bronte

{"title":"The roles of arginases and arginine in immunity","authors":"Stefania Canè, Roger Geiger, Vincenzo Bronte","doi":"10.1038/s41577-024-01098-2","DOIUrl":"10.1038/s41577-024-01098-2","url":null,"abstract":"Arginase activity and arginine metabolism in immune cells have important consequences for health and disease. Their dysregulation is commonly observed in cancer, autoimmune disorders and infectious diseases. Following the initial description of a role for arginase in the dysfunction of T cells mounting an antitumour response, numerous studies have broadened our understanding of the regulation and expression of arginases and their integration with other metabolic pathways. Here, we highlight the differences in arginase compartmentalization and storage between humans and rodents that should be taken into consideration when assessing the effects of arginase activity. We detail the roles of arginases, arginine and its metabolites in immune cells and their effects in the context of cancer, autoimmunity and infectious disease. Finally, we explore potential therapeutic strategies targeting arginases and arginine. This Review provides an overview of arginine and arginase function in immune cells, at the steady state and during disease. It considers the relevance of this pathway for metabolic, immune and genetic regulation, together with possible therapeutic interventions.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"266-284"},"PeriodicalIF":67.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448108","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}

引用次数: 0

The role of the AHR in host–pathogen interactions AHR 在宿主与病原体相互作用中的作用

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-10-16 DOI: 10.1038/s41577-024-01088-4

Palmira Barreira-Silva, Yilong Lian, Stefan H. E. Kaufmann, Pedro Moura-Alves

{"title":"The role of the AHR in host–pathogen interactions","authors":"Palmira Barreira-Silva, Yilong Lian, Stefan H. E. Kaufmann, Pedro Moura-Alves","doi":"10.1038/s41577-024-01088-4","DOIUrl":"10.1038/s41577-024-01088-4","url":null,"abstract":"Host–microorganism encounters take place in many different ways and with different types of outcomes. Three major types of microorganisms need to be distinguished: (1) pathogens that cause harm to the host and must be controlled; (2) environmental microorganisms that can be ignored but must be controlled at higher abundance; and (3) symbiotic microbiota that require support by the host. Recent evidence indicates that the aryl hydrocarbon receptor (AHR) senses and initiates signalling and gene expression in response to a plethora of microorganisms and infectious conditions. It was originally identified as a receptor that binds xenobiotics. However, it was subsequently found to have a critical role in numerous biological processes, including immunity and inflammation and was recently classified as a pattern recognition receptor. Here we review the role of the AHR in host–pathogen interactions, focusing on AHR sensing of different microbial classes, the ligands involved, responses elicited and disease outcomes. Moreover, we explore the therapeutic potential of targeting the AHR in the context of infection. The aryl hydrocarbon receptor (AHR) can sense and initiate immune responses to many different infectious organisms. Here, Moura-Alves and colleagues review the role of the AHR in host–pathogen interactions and explore the therapeutic potential of targeting the AHR in the context of different infectious diseases.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"178-194"},"PeriodicalIF":67.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439691","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}

引用次数: 0