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Immune-mediated strategies to solving the HIV reservoir problem 解决HIV病毒库问题的免疫介导策略
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-02-13 DOI: 10.1038/s41577-025-01136-7
Deanna A. Kulpa, Mirko Paiardini, Guido Silvestri
{"title":"Immune-mediated strategies to solving the HIV reservoir problem","authors":"Deanna A. Kulpa, Mirko Paiardini, Guido Silvestri","doi":"10.1038/s41577-025-01136-7","DOIUrl":"https://doi.org/10.1038/s41577-025-01136-7","url":null,"abstract":"<p>Antiretroviral therapy (ART) has markedly improved the life-expectancy of people living with HIV. However, during both HIV infection of humans and simian immunodeficiency virus infection of macaques, virus replication almost invariably rebounds upon ART interruption, due to the long-term persistency of a pool of latently infected cells harbouring integrated, replication-competent virus (known as the virus reservoir). Solving this ‘HIV reservoir problem’ is the key to achieving a cure (or at least a persistent remission) for HIV infection. Here, we summarize the key scientific evidence supporting the hypothesis that host immune responses, including those mediated by CD8<sup>+</sup> T cells, B cells, antibodies and innate immune cells, affect the size, clonality, and cellular, tissue and organ distribution of the HIV reservoir. Importantly, we believe that any solution to the ‘reservoir problem’ must address not only the multifaceted interactions between HIV and the host immune system, but also the complex interplay between the immunobiology of memory CD4<sup>+</sup> T helper cells (which form the main virus reservoir) and the molecular mechanisms that regulate HIV latency and reactivation. These concepts provide the rationale to develop new, immune-based approaches to ‘cure’ HIV infection; we review recent efforts to develop such therapies and their efficacy (or lack thereof) in disrupting the establishment and/or persistence of the virus reservoir in preclinical animal models and human clinical trials.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"8 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401370","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
HDAC9 association with heart disease linked to NLRP3 inflammasome activation HDAC9与NLRP3炎性体激活相关的心脏病
IF 67.7 1区 医学
Nature Reviews Immunology Pub Date : 2025-02-12 DOI: 10.1038/s41577-025-01144-7
Yvonne Bordon
{"title":"HDAC9 association with heart disease linked to NLRP3 inflammasome activation","authors":"Yvonne Bordon","doi":"10.1038/s41577-025-01144-7","DOIUrl":"10.1038/s41577-025-01144-7","url":null,"abstract":"Loss of a conserved cis-regulatory element at HDAC9 increases NLRP3 inflammasome activation and may explain why HDAC9 is a major risk locus for cardiovascular disease.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"157-157"},"PeriodicalIF":67.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393011","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
Faulty mitochondria jump between tumours and T cells 有缺陷的线粒体在肿瘤和T细胞之间跳跃
IF 67.7 1区 医学
Nature Reviews Immunology Pub Date : 2025-02-07 DOI: 10.1038/s41577-025-01143-8
Lucy Bird
{"title":"Faulty mitochondria jump between tumours and T cells","authors":"Lucy Bird","doi":"10.1038/s41577-025-01143-8","DOIUrl":"10.1038/s41577-025-01143-8","url":null,"abstract":"To evade elimination by T cells, tumour cells transfer mutant mitochondria to T cells, which reprogrammes their metabolism and compromises their antitumour activity.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"155-155"},"PeriodicalIF":67.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257886","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
B cells in non-lymphoid tissues 非淋巴组织中的B细胞
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-02-05 DOI: 10.1038/s41577-025-01137-6
Abrar Samiea, George Celis, Rashi Yadav, Lauren B. Rodda, Joshua M. Moreau
{"title":"B cells in non-lymphoid tissues","authors":"Abrar Samiea, George Celis, Rashi Yadav, Lauren B. Rodda, Joshua M. Moreau","doi":"10.1038/s41577-025-01137-6","DOIUrl":"https://doi.org/10.1038/s41577-025-01137-6","url":null,"abstract":"<p>B cells have long been understood to be drivers of both humoral and cellular immunity. Recent advances underscore this importance but also indicate that in infection, inflammatory disease and cancer, B cells function directly at sites of inflammation and form tissue-resident memory populations. The spatial organization and cellular niches of tissue B cells have profound effects on their function and on disease outcome, as well as on patient response to therapy. Here we review the role of B cells in peripheral tissues in homeostasis and disease, and discuss the newly identified cellular and molecular signals that are involved in regulating their activity. We integrate emerging data from multi-omic human studies with experimental models to propose a framework for B cell function in tissue inflammation and homeostasis.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"79 2 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192154","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
Inclusion of ACKR5 in the systematic nomenclature of atypical chemokine receptors 在非典型趋化因子受体的系统命名中包含ACKR5
IF 67.7 1区 医学
Nature Reviews Immunology Pub Date : 2025-02-03 DOI: 10.1038/s41577-025-01135-8
Martyna Szpakowska, Daniel F. Legler, Stefan Offermanns, Silvano Sozzani, Antal Rot, Marcus Thelen, Andy Chevigné
{"title":"Inclusion of ACKR5 in the systematic nomenclature of atypical chemokine receptors","authors":"Martyna Szpakowska,&nbsp;Daniel F. Legler,&nbsp;Stefan Offermanns,&nbsp;Silvano Sozzani,&nbsp;Antal Rot,&nbsp;Marcus Thelen,&nbsp;Andy Chevigné","doi":"10.1038/s41577-025-01135-8","DOIUrl":"10.1038/s41577-025-01135-8","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"225-226"},"PeriodicalIF":67.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41577-025-01135-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077293","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}
引用次数: 0
Podoplanin mediates stromal–immune crosstalk in the lymph node Podoplanin介导淋巴结间质免疫串扰
IF 67.7 1区 医学
Nature Reviews Immunology Pub Date : 2025-01-31 DOI: 10.1038/s41577-025-01140-x
Erika E. McCartney, Matthew B. Buechler
{"title":"Podoplanin mediates stromal–immune crosstalk in the lymph node","authors":"Erika E. McCartney,&nbsp;Matthew B. Buechler","doi":"10.1038/s41577-025-01140-x","DOIUrl":"10.1038/s41577-025-01140-x","url":null,"abstract":"A preprint by Makris et al. shows that podoplanin is a key regulator of the functions of fibroblastic reticular cells in lymph nodes, by modulating interactions with immune cells.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"160-160"},"PeriodicalIF":67.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071395","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
Immune control of brain physiology 脑生理学的免疫控制
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-01-31 DOI: 10.1038/s41577-025-01129-6
Mariángeles Kovacs, Amaia Dominguez-Belloso, Samir Ali-Moussa, Aleksandra Deczkowska
{"title":"Immune control of brain physiology","authors":"Mariángeles Kovacs, Amaia Dominguez-Belloso, Samir Ali-Moussa, Aleksandra Deczkowska","doi":"10.1038/s41577-025-01129-6","DOIUrl":"https://doi.org/10.1038/s41577-025-01129-6","url":null,"abstract":"<p>The peripheral immune system communicates with the brain through complex anatomical routes involving the skull, the brain borders, circumventricular organs and peripheral nerves. These immune–brain communication pathways were classically considered to be dormant under physiological conditions and active only in cases of infection or damage. Yet, peripheral immune cells and signals are key in brain development, function and maintenance. In this Perspective, we propose an alternative framework for understanding the mechanisms of immune–brain communication. During brain development and in homeostasis, these anatomical structures allow selected elements of the peripheral immune system to affect the brain directly or indirectly, within physiological limits. By contrast, in ageing and pathological settings, detrimental peripheral immune signals hijack the existing communication routes or alter their structure. We discuss why a diversity of communication channels is needed and how they work in relation to one another to maintain homeostasis of the brain.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"74 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071406","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
Trained immunity in chronic inflammatory diseases and cancer 慢性炎症性疾病和癌症的训练免疫
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-01-31 DOI: 10.1038/s41577-025-01132-x
George Hajishengallis, Mihai G. Netea, Triantafyllos Chavakis
{"title":"Trained immunity in chronic inflammatory diseases and cancer","authors":"George Hajishengallis, Mihai G. Netea, Triantafyllos Chavakis","doi":"10.1038/s41577-025-01132-x","DOIUrl":"https://doi.org/10.1038/s41577-025-01132-x","url":null,"abstract":"<p>A decade after the term ‘trained immunity’ (TRIM) was coined to reflect the long-lasting hyper-responsiveness of innate immune cells with an epigenetically imprinted ‘memory’ of earlier stimuli, our understanding has broadened to include the potential implications of TRIM in health and disease. Here, after summarizing the well-documented beneficial effects of TRIM against infections, we discuss emerging evidence that TRIM is also a major underlying mechanism in chronic inflammation-related disorders such as periodontitis, rheumatoid arthritis and cardiovascular disease. Furthermore, mounting evidence indicates that the induction of TRIM by certain agonists confers protective antitumour responses. Although the mechanisms underlying TRIM require further study, the current knowledge enables the experimental development of innovative therapeutic approaches to stimulate or inhibit TRIM in a context-appropriate manner, such as the stimulation of TRIM in cancer or its inhibition in inflammatory disorders.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"122 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071396","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
Kidney immunology from pathophysiology to clinical translation 肾免疫学从病理生理学到临床的转化
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-01-30 DOI: 10.1038/s41577-025-01131-y
Christian Kurts, Sibylle von Vietinghoff, Christian F. Krebs, Ulf Panzer
{"title":"Kidney immunology from pathophysiology to clinical translation","authors":"Christian Kurts, Sibylle von Vietinghoff, Christian F. Krebs, Ulf Panzer","doi":"10.1038/s41577-025-01131-y","DOIUrl":"https://doi.org/10.1038/s41577-025-01131-y","url":null,"abstract":"<p>Kidney diseases are widespread and represent a considerable medical, social and economic burden. However, there has been marked progress in understanding the immunological aspects of kidney disease. This includes the identification of distinct intrarenal immunological niches and characterization of kidney disease endotypes according to the underlying molecular immunopathology, as well as a better understanding of the pathological roles for T cells, mononuclear phagocytes and B cells and the renal elements they target. These insights have improved the diagnosis of kidney disease. Here, we discuss new developments in our understanding of kidney immunology, focusing on immune mechanisms of disease and their translational implications for the diagnosis and treatment of kidney disease. We also describe the immune-mediated crosstalk between the kidney and other organs that influences kidney disease and extrarenal inflammation.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"28 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057117","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
Biomolecular condensates in immune cell fate 免疫细胞命运中的生物分子凝聚
IF 100.3 1区 医学
Nature Reviews Immunology Pub Date : 2025-01-28 DOI: 10.1038/s41577-025-01130-z
Srikanth Kodali, Caroline M. Sands, Lei Guo, Yun Huang, Bruno Di Stefano
{"title":"Biomolecular condensates in immune cell fate","authors":"Srikanth Kodali, Caroline M. Sands, Lei Guo, Yun Huang, Bruno Di Stefano","doi":"10.1038/s41577-025-01130-z","DOIUrl":"https://doi.org/10.1038/s41577-025-01130-z","url":null,"abstract":"<p>Fate decisions during immune cell development require temporally precise changes in gene expression. Evidence suggests that the dynamic modulation of these changes is associated with the formation of diverse, membrane-less nucleoprotein assemblies that are termed biomolecular condensates. These condensates are thought to orchestrate fate-determining transcriptional and post-transcriptional processes by locally and transiently concentrating DNA or RNA molecules alongside their regulatory proteins. Findings have established a link between condensate formation and the gene regulatory networks that ensure the proper development of immune cells. Conversely, condensate dysregulation has been linked to impaired immune cell fates, including ageing and malignant transformation. This Review explores the putative mechanistic links between condensate assembly and the gene regulatory frameworks that govern normal and pathological development in the immune system.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"67 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049989","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
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