{"title":"Reduced duration of natural protection in the Omicron era","authors":"Alexandra Flemming","doi":"10.1038/s41577-025-01145-6","DOIUrl":"10.1038/s41577-025-01145-6","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"156-156"},"PeriodicalIF":67.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417699","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}
{"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":"10.1038/s41577-025-01136-7","url":null,"abstract":"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+ 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+ 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. HIV infection persists under antiretroviral therapy due to a reservoir of latently infected cells. This Perspective discusses how host immune responses might affect the establishment and persistence of the viral reservoir, an understanding of which supports the development of immune-based approaches to ‘cure’ HIV infection by disrupting the reservoir.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 7","pages":"542-553"},"PeriodicalIF":60.9,"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}
{"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}
{"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}
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":"10.1038/s41577-025-01137-6","url":null,"abstract":"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. B cells are major drivers of systemic immunity, but they also act locally in non-lymphoid organs. This Review highlights new insights into mechanisms of tissue B cell function as well as efforts to leverage this biology for immunotherapy.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 7","pages":"483-496"},"PeriodicalIF":60.9,"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}
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, Daniel F. Legler, Stefan Offermanns, Silvano Sozzani, Antal Rot, Marcus Thelen, 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}
{"title":"Podoplanin mediates stromal–immune crosstalk in the lymph node","authors":"Erika E. McCartney, 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}
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":"10.1038/s41577-025-01129-6","url":null,"abstract":"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. The peripheral immune system communicates with the brain through diverse anatomical routes to shape brain physiology. Here we discuss why such diversity is needed and explore how these routes are leveraged during development and hijacked in ageing.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 7","pages":"515-527"},"PeriodicalIF":60.9,"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}
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":"10.1038/s41577-025-01132-x","url":null,"abstract":"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. Besides its beneficial effects against infection, trained immunity has recently been implicated in inflammation-related disorders and is being exploited in cancer immunotherapy. These advances may enable the development of therapeutic interventions to modulate trained immunity towards promoting human health.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 7","pages":"497-514"},"PeriodicalIF":60.9,"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}