Pub Date : 2024-02-23DOI: 10.1038/s41577-024-01009-5
Zülal Cibir, Matthias Gunzer
In this Tools of the Trade article, Zülal Cibir and Matthias Gunzer introduce their multi-lens array microscope called ComplexEye that allows high-throughput analysis of cell migration.
{"title":"ComplexEye: a multi-lens array microscope for high-throughput cell migration analysis","authors":"Zülal Cibir, Matthias Gunzer","doi":"10.1038/s41577-024-01009-5","DOIUrl":"10.1038/s41577-024-01009-5","url":null,"abstract":"In this Tools of the Trade article, Zülal Cibir and Matthias Gunzer introduce their multi-lens array microscope called ComplexEye that allows high-throughput analysis of cell migration.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":100.3,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139938768","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 : 2024-02-21DOI: 10.1038/s41577-024-00996-9
Katherine S. Forsyth, Nikhil Jiwrajka, Claudia D. Lovell, Natalie E. Toothacre, Montserrat C. Anguera
There are notable sex-based differences in immune responses to pathogens and self-antigens, with female individuals exhibiting increased susceptibility to various autoimmune diseases, and male individuals displaying preferential susceptibility to some viral, bacterial, parasitic and fungal infections. Although sex hormones clearly contribute to sex differences in immune cell composition and function, the presence of two X chromosomes in female individuals suggests that differential gene expression of numerous X chromosome-linked immune-related genes may also influence sex-biased innate and adaptive immune cell function in health and disease. Here, we review the sex differences in immune system composition and function, examining how hormones and genetics influence the immune system. We focus on the genetic and epigenetic contributions responsible for altered X chromosome-linked gene expression, and how this impacts sex-biased immune responses in the context of pathogen infection and systemic autoimmunity. Immune responses to pathogens and self-antigens show sex-based differences, with female individuals generally more susceptible to autoimmunity and male individuals more vulnerable to infections. In this Review, the authors explore the role of hormones and genetics in shaping immune responses, and discuss genetic and epigenetic contributions to altered X-linked gene expression that affect immune responses.
对病原体和自身抗原的免疫反应存在明显的性别差异，女性对各种自身免疫性疾病的易感性增加，而男性对某些病毒、细菌、寄生虫和真菌感染的易感性较高。虽然性激素明显导致了免疫细胞组成和功能的性别差异，但女性个体中存在两条 X 染色体，这表明与 X 染色体相关的大量免疫相关基因的不同基因表达也可能影响健康和疾病中先天性和适应性免疫细胞功能的性别差异。在此，我们回顾了免疫系统组成和功能的性别差异，探讨了激素和遗传是如何影响免疫系统的。我们重点研究了导致 X 染色体相关基因表达改变的遗传学和表观遗传学因素，以及这在病原体感染和系统性自身免疫的情况下如何影响性别免疫反应。
{"title":"The conneXion between sex and immune responses","authors":"Katherine S. Forsyth, Nikhil Jiwrajka, Claudia D. Lovell, Natalie E. Toothacre, Montserrat C. Anguera","doi":"10.1038/s41577-024-00996-9","DOIUrl":"10.1038/s41577-024-00996-9","url":null,"abstract":"There are notable sex-based differences in immune responses to pathogens and self-antigens, with female individuals exhibiting increased susceptibility to various autoimmune diseases, and male individuals displaying preferential susceptibility to some viral, bacterial, parasitic and fungal infections. Although sex hormones clearly contribute to sex differences in immune cell composition and function, the presence of two X chromosomes in female individuals suggests that differential gene expression of numerous X chromosome-linked immune-related genes may also influence sex-biased innate and adaptive immune cell function in health and disease. Here, we review the sex differences in immune system composition and function, examining how hormones and genetics influence the immune system. We focus on the genetic and epigenetic contributions responsible for altered X chromosome-linked gene expression, and how this impacts sex-biased immune responses in the context of pathogen infection and systemic autoimmunity. Immune responses to pathogens and self-antigens show sex-based differences, with female individuals generally more susceptible to autoimmunity and male individuals more vulnerable to infections. In this Review, the authors explore the role of hormones and genetics in shaping immune responses, and discuss genetic and epigenetic contributions to altered X-linked gene expression that affect immune responses.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139917147","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 : 2024-02-19DOI: 10.1038/s41577-024-00994-x
Tomokazu S. Sumida, Nardos T. Cheru, David A. Hafler
The discovery of FOXP3+ regulatory T (Treg) cells as a distinct cell lineage with a central role in regulating immune responses provided a deeper understanding of self-tolerance. The transcription factor FOXP3 serves a key role in Treg cell lineage determination and maintenance, but is not sufficient to enable the full potential of Treg cell suppression, indicating that other factors orchestrate the fine-tuning of Treg cell function. Moreover, FOXP3-independent mechanisms have recently been shown to contribute to Treg cell dysfunction. FOXP3 mutations in humans cause lethal fulminant systemic autoinflammation (IPEX syndrome). However, it remains unclear to what degree Treg cell dysfunction is contributing to the pathophysiology of common autoimmune diseases. In this Review, we discuss the origins of Treg cells in the periphery and the multilayered mechanisms by which Treg cells are induced, as well as the FOXP3-dependent and FOXP3-independent cellular programmes that maintain the suppressive function of Treg cells in humans and mice. Further, we examine evidence for Treg cell dysfunction in the context of common autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis. In this Review, the authors discuss the origins of regulatory T (Treg) cells in the periphery and the mechanisms by which Treg cells are induced, as well as the regulation of the suppressive function of these cells. Moreover, they examine evidence for and mechanisms of Treg cell dysfunction in common autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis.
{"title":"The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases","authors":"Tomokazu S. Sumida, Nardos T. Cheru, David A. Hafler","doi":"10.1038/s41577-024-00994-x","DOIUrl":"10.1038/s41577-024-00994-x","url":null,"abstract":"The discovery of FOXP3+ regulatory T (Treg) cells as a distinct cell lineage with a central role in regulating immune responses provided a deeper understanding of self-tolerance. The transcription factor FOXP3 serves a key role in Treg cell lineage determination and maintenance, but is not sufficient to enable the full potential of Treg cell suppression, indicating that other factors orchestrate the fine-tuning of Treg cell function. Moreover, FOXP3-independent mechanisms have recently been shown to contribute to Treg cell dysfunction. FOXP3 mutations in humans cause lethal fulminant systemic autoinflammation (IPEX syndrome). However, it remains unclear to what degree Treg cell dysfunction is contributing to the pathophysiology of common autoimmune diseases. In this Review, we discuss the origins of Treg cells in the periphery and the multilayered mechanisms by which Treg cells are induced, as well as the FOXP3-dependent and FOXP3-independent cellular programmes that maintain the suppressive function of Treg cells in humans and mice. Further, we examine evidence for Treg cell dysfunction in the context of common autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis. In this Review, the authors discuss the origins of regulatory T (Treg) cells in the periphery and the mechanisms by which Treg cells are induced, as well as the regulation of the suppressive function of these cells. Moreover, they examine evidence for and mechanisms of Treg cell dysfunction in common autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906134","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 : 2024-02-19DOI: 10.1038/s41577-024-00995-w
Jianing Fu, Kate Schroder, Hao Wu
Inflammasomes are supramolecular complexes that form in the cytosol in response to pathogen-associated and damage-associated stimuli, as well as other danger signals that perturb cellular homoeostasis, resulting in host defence responses in the form of cytokine release and programmed cell death (pyroptosis). Inflammasome activity is closely associated with numerous human disorders, including rare genetic syndromes of autoinflammation, cardiovascular diseases, neurodegeneration and cancer. In recent years, a range of inflammasome components and their functions have been discovered, contributing to our knowledge of the overall machinery. Here, we review the latest advances in inflammasome biology from the perspective of structural and mechanistic studies. We focus on the most well-studied components of the canonical inflammasome — NAIP–NLRC4, NLRP3, NLRP1, CARD8 and caspase-1 — as well as caspase-4, caspase-5 and caspase-11 of the noncanonical inflammasome, and the inflammasome effectors GSDMD and NINJ1. These structural studies reveal important insights into how inflammasomes are assembled and regulated, and how they elicit the release of IL-1 family cytokines and induce membrane rupture in pyroptosis. This Review highlights new insights into the biology of inflammasomes from the perspective of structural and mechanistic studies, revealing how the supramolecular complexes that activate inflammatory caspases are assembled and regulated, to induce cytokine maturation and release, as well as pyroptotic cell death.
{"title":"Mechanistic insights from inflammasome structures","authors":"Jianing Fu, Kate Schroder, Hao Wu","doi":"10.1038/s41577-024-00995-w","DOIUrl":"10.1038/s41577-024-00995-w","url":null,"abstract":"Inflammasomes are supramolecular complexes that form in the cytosol in response to pathogen-associated and damage-associated stimuli, as well as other danger signals that perturb cellular homoeostasis, resulting in host defence responses in the form of cytokine release and programmed cell death (pyroptosis). Inflammasome activity is closely associated with numerous human disorders, including rare genetic syndromes of autoinflammation, cardiovascular diseases, neurodegeneration and cancer. In recent years, a range of inflammasome components and their functions have been discovered, contributing to our knowledge of the overall machinery. Here, we review the latest advances in inflammasome biology from the perspective of structural and mechanistic studies. We focus on the most well-studied components of the canonical inflammasome — NAIP–NLRC4, NLRP3, NLRP1, CARD8 and caspase-1 — as well as caspase-4, caspase-5 and caspase-11 of the noncanonical inflammasome, and the inflammasome effectors GSDMD and NINJ1. These structural studies reveal important insights into how inflammasomes are assembled and regulated, and how they elicit the release of IL-1 family cytokines and induce membrane rupture in pyroptosis. This Review highlights new insights into the biology of inflammasomes from the perspective of structural and mechanistic studies, revealing how the supramolecular complexes that activate inflammatory caspases are assembled and regulated, to induce cytokine maturation and release, as well as pyroptotic cell death.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906133","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 : 2024-02-13DOI: 10.1038/s41577-024-01007-7
Maria Papatriantafyllou
{"title":"Low risk of CAR T cells going rogue","authors":"Maria Papatriantafyllou","doi":"10.1038/s41577-024-01007-7","DOIUrl":"10.1038/s41577-024-01007-7","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":100.3,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139728189","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 : 2024-02-13DOI: 10.1038/s41577-024-01004-w
Yvonne Bordon
Regulatory T cells have pathological roles in driving fibrosis and insulin resistance in the setting of non-alcoholic steatohepatitis.
调节性 T 细胞在非酒精性脂肪性肝炎的纤维化和胰岛素抵抗中起着病理作用。
{"title":"Regulation goes awry in the liver","authors":"Yvonne Bordon","doi":"10.1038/s41577-024-01004-w","DOIUrl":"10.1038/s41577-024-01004-w","url":null,"abstract":"Regulatory T cells have pathological roles in driving fibrosis and insulin resistance in the setting of non-alcoholic steatohepatitis.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":100.3,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139727964","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 : 2024-02-12DOI: 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":null,"pages":null},"PeriodicalIF":100.3,"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}
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