Nature Reviews Immunology最新文献_第9页

Mitochondrial tonic for adoptive T cell therapies 采用 T 细胞疗法的线粒体补药。

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-20 DOI: 10.1038/s41577-024-01095-5

Kirsty Minton

引用次数: 0

Antigen presentation for central tolerance induction 诱导中枢耐受的抗原递呈

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-18 DOI: 10.1038/s41577-024-01076-8

Ludger Klein, Elisabetta Petrozziello

{"title":"Antigen presentation for central tolerance induction","authors":"Ludger Klein, Elisabetta Petrozziello","doi":"10.1038/s41577-024-01076-8","DOIUrl":"10.1038/s41577-024-01076-8","url":null,"abstract":"The extent of central T cell tolerance is determined by the diversity of self-antigens that developing thymocytes ‘see’ on thymic antigen-presenting cells (APCs). Here, focusing on insights from the past decade, we review the functional adaptations of medullary thymic epithelial cells, thymic dendritic cells and thymic B cells for the purpose of tolerance induction. Their distinct cellular characteristics range from unconventional phenomena, such as promiscuous gene expression or mimicry of peripheral cell types, to strategic positioning in distinct microenvironments and divergent propensities to preferentially access endogenous or exogenous antigen pools. We also discuss how ‘tonic’ inflammatory signals in the thymic microenvironment may extend the intrathymically visible ‘self’ to include autoantigens that are otherwise associated with highly immunogenic peripheral environments. For effective central T cell tolerance, developing thymocytes must encounter a diverse range of self-antigens presented by various thymic cells. Here, the authors describe how medullary thymic epithelial cells, dendritic cells and B cells are uniquely adapted through promiscuous gene expression, strategic positioning and inflammatory signals, which shape the peptide–MHC ligandomes and extend self-antigen visibility in the thymic microenvironment.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 1","pages":"57-72"},"PeriodicalIF":67.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236286","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

Inducible antibacterial responses in macrophages 巨噬细胞中的诱导抗菌反应

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-18 DOI: 10.1038/s41577-024-01080-y

Matthew J. Sweet, Divya Ramnath, Amit Singhal, Ronan Kapetanovic

{"title":"Inducible antibacterial responses in macrophages","authors":"Matthew J. Sweet, Divya Ramnath, Amit Singhal, Ronan Kapetanovic","doi":"10.1038/s41577-024-01080-y","DOIUrl":"10.1038/s41577-024-01080-y","url":null,"abstract":"Macrophages destroy bacteria and other microorganisms through phagocytosis-coupled antimicrobial responses, such as the generation of reactive oxygen species and the delivery of hydrolytic enzymes from lysosomes to the phagosome. However, many intracellular bacteria subvert these responses, escaping to other cellular compartments to survive and/or replicate. Such bacterial subversion strategies are countered by a range of additional direct antibacterial responses that are switched on by pattern-recognition receptors and/or host-derived cytokines and other factors, often through inducible gene expression and/or metabolic reprogramming. Our understanding of these inducible antibacterial defence strategies in macrophages is rapidly evolving. In this Review, we provide an overview of the broad repertoire of antibacterial responses that can be engaged in macrophages, including LC3-associated phagocytosis, metabolic reprogramming and antimicrobial metabolites, lipid droplets, guanylate-binding proteins, antimicrobial peptides, metal ion toxicity, nutrient depletion, autophagy and nitric oxide production. We also highlight key inducers, signalling pathways and transcription factors involved in driving these different antibacterial responses. Finally, we discuss how a detailed understanding of the molecular mechanisms of antibacterial responses in macrophages might be exploited for developing host-directed therapies to combat antibiotic-resistant bacterial infections. Macrophages are innate immune sentinels providing frontline defence against infection. This Review describes the inducible mechanisms used by macrophages to kill bacterial pathogens and/or inhibit their growth and outlines how this knowledge might be exploited in the design of host-directed therapies.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 2","pages":"92-107"},"PeriodicalIF":67.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245305","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

Striking a balance: new perspectives on homeostatic dendritic cell maturation 取得平衡：树突状细胞成熟的新视角

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-17 DOI: 10.1038/s41577-024-01079-5

Victor Bosteels, Sophie Janssens

{"title":"Striking a balance: new perspectives on homeostatic dendritic cell maturation","authors":"Victor Bosteels, Sophie Janssens","doi":"10.1038/s41577-024-01079-5","DOIUrl":"10.1038/s41577-024-01079-5","url":null,"abstract":"Dendritic cells (DCs) are crucial gatekeepers of the balance between immunity and tolerance. They exist in two functional states, immature or mature, that refer to an information-sensing versus an information-transmitting state, respectively. Historically, the term DC maturation was used to describe the acquisition of immunostimulatory capacity by DCs following their triggering by pathogens or tissue damage signals. As such, immature DCs were proposed to mediate tolerance, whereas mature DCs were associated with the induction of protective T cell immunity. Later studies have challenged this view and unequivocally demonstrated that two distinct modes of DC maturation exist, homeostatic and immunogenic DC maturation, each with a distinct functional outcome. Therefore, the mere expression of maturation markers cannot be used to predict immunogenicity. How DCs become activated in homeostatic conditions and maintain tolerance remains an area of intense debate. Several recent studies have shed light on the signals driving the homeostatic maturation programme, especially in the conventional type 1 DC (cDC1) compartment. Here, we highlight our growing understanding of homeostatic DC maturation and the relevance of this process for immune tolerance. Dendritic cells (DCs) act as gatekeepers between immunity and tolerance. Initially, it was postulated that mature DCs promote effector T cell responses and immature DCs promote tolerance. Recent studies have shown instead that two distinct modes of DC maturation exist — homeostatic and immunogenic. Here, Bosteels and Janssens discuss our current understanding of homeostatic DC maturation and how this contributes to immune tolerance, with a focus on the cDC1 compartment.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 2","pages":"125-140"},"PeriodicalIF":67.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236287","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

Mast cell BH4–serotonin metabolic network implicated in postoperative pain 与术后疼痛有关的肥大细胞 BH4-羟色胺代谢网络

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-16 DOI: 10.1038/s41577-024-01089-3

Alexandra Flemming

引用次数: 0

Using art and history to communicate immunology to a broad audience 利用艺术和历史向广大受众传播免疫学知识

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-16 DOI: 10.1038/s41577-024-01090-w

Francesca Di Rosa

引用次数: 0

Publisher Correction: Immunological studies in trans-individuals undergoing gender affirming hormone therapy 出版商更正：对接受性别平权激素治疗的变性人进行免疫学研究。

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-10 DOI: 10.1038/s41577-024-01092-8

Anna James, Petter Brodin

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Towards a unifying model for B-cell receptor triggering 为 B 细胞受体触发建立统一模型

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-10 DOI: 10.1038/s41577-024-01073-x

Søren E. Degn, Pavel Tolar

{"title":"Towards a unifying model for B-cell receptor triggering","authors":"Søren E. Degn, Pavel Tolar","doi":"10.1038/s41577-024-01073-x","DOIUrl":"10.1038/s41577-024-01073-x","url":null,"abstract":"Antibodies are exceptionally versatile molecules with remarkable flexibility in their binding properties. Their natural targets range from small-molecule toxins, across viruses of different sizes, to bacteria and large multicellular parasites. The molecular determinants bound by antibodies include proteins, peptides, carbohydrates, nucleic acids, lipids and even synthetic molecules that have never existed in nature. Membrane-anchored antibodies also serve as receptors on the surface of the B cells that produce them. Despite recent structural insights, there is still no unifying molecular mechanism to explain how antibody targets (antigens) trigger the activation of these B-cell receptors (BCRs). After cognate antigen encounter, somatic hypermutation and class-switch recombination allow BCR affinity maturation and immunoglobulin class-specific responses, respectively. This raises the fundamental question of how one receptor activation mechanism can accommodate a plethora of variant receptors and ligands, and how it can ensure that individual B cells remain responsive to antigen after somatic hypermutation and class switching. There is still no definite answer. Here we give a brief historical account of the different models proposed to explain BCR triggering and discuss their merit in the context of the current knowledge of the structure of BCRs, their dynamic membrane distribution, and recent biochemical and cell biological insights. The mechanisms by which antigen triggers B-cell activation are incompletely understood. In this Review, Degn and Tolar discuss the different models of B-cell receptor triggering that have been proposed over the years in the light of recent insights.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 2","pages":"77-91"},"PeriodicalIF":67.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160452","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

Inflammasome components as new therapeutic targets in inflammatory disease 作为炎症性疾病新治疗靶点的炎症体成分

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-09 DOI: 10.1038/s41577-024-01075-9

Rebecca C. Coll, Kate Schroder

{"title":"Inflammasome components as new therapeutic targets in inflammatory disease","authors":"Rebecca C. Coll, Kate Schroder","doi":"10.1038/s41577-024-01075-9","DOIUrl":"10.1038/s41577-024-01075-9","url":null,"abstract":"Inflammation drives pathology in many human diseases for which there are no disease-modifying drugs. Inflammasomes are signalling platforms that can induce pathological inflammation and tissue damage, having potential as an exciting new class of drug targets. Small-molecule inhibitors of the NLRP3 inflammasome that are now in clinical trials have demonstrated proof of concept that inflammasomes are druggable, and so drug development programmes are now focusing on other key inflammasome molecules. In this Review, we describe the potential of inflammasome components as candidate drug targets and the novel inflammasome inhibitors that are being developed. We discuss how the signalling biology of inflammasomes offers mechanistic insights for therapeutic targeting. We also discuss the major scientific and technical challenges associated with drugging these molecules during preclinical development and clinical trials. Inflammasomes are signalling machines that drive inflammation. This Review highlights the signalling biology of inflammasomes and how we can use small molecules or biologics to block pathological inflammasome signalling to treat or prevent diverse human diseases.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 1","pages":"22-41"},"PeriodicalIF":67.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160454","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

Have a cake and eat it too: the importance of metaphors in research communication 既吃蛋糕又吃蛋糕：隐喻在科研交流中的重要性

IF 67.7 1区医学

Nature Reviews Immunology Pub Date : 2024-09-09 DOI: 10.1038/s41577-024-01085-7

Anne Spurkland

引用次数: 0