Pub Date : 2024-04-03DOI: 10.1038/s41423-024-01155-9
Qianjin Liu, Lijin Jiao, Mao-Sen Ye, Zhiyu Ma, Jinsong Yu, Ling-Yan Su, Wei-Yin Zou, Lu-Xiu Yang, Chang Chen, Yong-Gang Yao
Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases. However, the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown. In this study, we demonstrated that S-nitrosoglutathione reductase (GSNOR) deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1β expression levels and interleukin-1β (IL-1β) secretion in response to NLRP3 inflammasome stimulation. Furthermore, in vivo experiments utilizing Gsnor−/− mice revealed increased disease severity in both lipopolysaccharide (LPS)-induced septic shock and dextran sodium sulfate (DSS)-induced colitis models. Additionally, we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor−/− Nlrp3−/− double-knockout (DKO) mice. Mechanistically, GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14 (MAPK14) at the Cys211 residue and augments MAPK14 kinase activity, thereby promoting Nlrp3 and Il-1β transcription and stimulating NLRP3 inflammasome activity. Our findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.
{"title":"GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14","authors":"Qianjin Liu, Lijin Jiao, Mao-Sen Ye, Zhiyu Ma, Jinsong Yu, Ling-Yan Su, Wei-Yin Zou, Lu-Xiu Yang, Chang Chen, Yong-Gang Yao","doi":"10.1038/s41423-024-01155-9","DOIUrl":"10.1038/s41423-024-01155-9","url":null,"abstract":"Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases. However, the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown. In this study, we demonstrated that S-nitrosoglutathione reductase (GSNOR) deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1β expression levels and interleukin-1β (IL-1β) secretion in response to NLRP3 inflammasome stimulation. Furthermore, in vivo experiments utilizing Gsnor−/− mice revealed increased disease severity in both lipopolysaccharide (LPS)-induced septic shock and dextran sodium sulfate (DSS)-induced colitis models. Additionally, we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor−/− Nlrp3−/− double-knockout (DKO) mice. Mechanistically, GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14 (MAPK14) at the Cys211 residue and augments MAPK14 kinase activity, thereby promoting Nlrp3 and Il-1β transcription and stimulating NLRP3 inflammasome activity. Our findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581781","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 : 2024-04-02DOI: 10.1038/s41423-024-01148-8
Sicong Ma, Yanan Ming, Jingxia Wu, Guoliang Cui
T cells are an important component of adaptive immunity and protect the host from infectious diseases and cancers. However, uncontrolled T cell immunity may cause autoimmune disorders. In both situations, antigen-specific T cells undergo clonal expansion upon the engagement and activation of antigens. Cellular metabolism is reprogrammed to meet the increase in bioenergetic and biosynthetic demands associated with effector T cell expansion. Metabolites not only serve as building blocks or energy sources to fuel cell growth and expansion but also regulate a broad spectrum of cellular signals that instruct the differentiation of multiple T cell subsets. The realm of immunometabolism research is undergoing swift advancements. Encapsulating all the recent progress within this concise review in not possible. Instead, our objective is to provide a succinct introduction to this swiftly progressing research, concentrating on the metabolic intricacies of three pivotal nutrient classes—lipids, glucose, and amino acids—in T cells. We shed light on recent investigations elucidating the roles of these three groups of metabolites in mediating the metabolic and immune functions of T cells. Moreover, we delve into the prospect of “editing” metabolic pathways within T cells using pharmacological or genetic approaches, with the aim of synergizing this approach with existing immunotherapies and enhancing the efficacy of antitumor and antiinfection immune responses.
T 细胞是适应性免疫的重要组成部分，能保护宿主免受传染病和癌症的侵袭。然而，不受控制的 T 细胞免疫可能会导致自身免疫性疾病。在这两种情况下，抗原特异性 T 细胞在接触和激活抗原后都会发生克隆扩增。细胞代谢被重新编程，以满足与效应 T 细胞扩增相关的生物能和生物合成需求的增加。代谢物不仅是促进细胞生长和扩增的构件或能量来源，还能调节多种细胞信号，指导多个 T 细胞亚群的分化。免疫代谢研究领域正在迅速发展。我们不可能在这篇简明扼要的综述中囊括所有最新进展。相反，我们的目标是简明扼要地介绍这项进展迅速的研究，集中探讨 T 细胞中三种关键营养物质--脂质、葡萄糖和氨基酸--代谢的复杂性。我们阐明了最近的研究，这些研究阐明了这三类代谢物在介导 T 细胞代谢和免疫功能方面的作用。此外，我们还深入探讨了利用药理学或遗传学方法 "编辑 "T 细胞内代谢途径的前景，目的是使这种方法与现有的免疫疗法协同增效，提高抗肿瘤和抗感染免疫反应的疗效。
{"title":"Cellular metabolism regulates the differentiation and function of T-cell subsets","authors":"Sicong Ma, Yanan Ming, Jingxia Wu, Guoliang Cui","doi":"10.1038/s41423-024-01148-8","DOIUrl":"10.1038/s41423-024-01148-8","url":null,"abstract":"T cells are an important component of adaptive immunity and protect the host from infectious diseases and cancers. However, uncontrolled T cell immunity may cause autoimmune disorders. In both situations, antigen-specific T cells undergo clonal expansion upon the engagement and activation of antigens. Cellular metabolism is reprogrammed to meet the increase in bioenergetic and biosynthetic demands associated with effector T cell expansion. Metabolites not only serve as building blocks or energy sources to fuel cell growth and expansion but also regulate a broad spectrum of cellular signals that instruct the differentiation of multiple T cell subsets. The realm of immunometabolism research is undergoing swift advancements. Encapsulating all the recent progress within this concise review in not possible. Instead, our objective is to provide a succinct introduction to this swiftly progressing research, concentrating on the metabolic intricacies of three pivotal nutrient classes—lipids, glucose, and amino acids—in T cells. We shed light on recent investigations elucidating the roles of these three groups of metabolites in mediating the metabolic and immune functions of T cells. Moreover, we delve into the prospect of “editing” metabolic pathways within T cells using pharmacological or genetic approaches, with the aim of synergizing this approach with existing immunotherapies and enhancing the efficacy of antitumor and antiinfection immune responses.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01148-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602086","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}
Pub Date : 2024-03-27DOI: 10.1038/s41423-024-01141-1
Xiaojing Liu, Fei-Long Meng
{"title":"Defining two subpopulations of marginal zone B cells","authors":"Xiaojing Liu, Fei-Long Meng","doi":"10.1038/s41423-024-01141-1","DOIUrl":"10.1038/s41423-024-01141-1","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305065","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 : 2024-03-26DOI: 10.1038/s41423-024-01152-y
Yu Chen, Yan Song, Zhe Wang, Yangfan Lai, Wei Yin, Qian Cai, Miaomiao Han, Yiheng Cai, Yushan Xue, Zhengrong Chen, Xi Li, Jing Chen, Min Li, Huabin Li, Rui He
The skin is the most common site of Staphylococcus aureus infection, which can lead to various diseases, including invasive and life-threatening infections, through evasion of host defense. However, little is known about the host factors that facilitate the innate immune evasion of S. aureus in the skin. Chemerin, which is abundantly expressed in the skin and can be activated by proteases derived from S. aureus, has both direct bacteria-killing activity and immunomodulatory effects via interactions with its receptor CMKLR1. Here, we demonstrate that a lack of the chemerin/CMKLR1 axis increases the neutrophil-mediated host defense against S. aureus in a mouse model of cutaneous infection, whereas chemerin overexpression, which mimics high levels of chemerin in obese individuals, exacerbates S. aureus cutaneous infection. Mechanistically, we identified keratinocytes that express CMKLR1 as the main target of chemerin to suppress S. aureus-induced IL-33 expression, leading to impaired skin neutrophilia and bacterial clearance. CMKLR1 signaling specifically inhibits IL-33 expression induced by cell wall components but not secreted proteins of S. aureus by inhibiting Akt activation in mouse keratinocytes. Thus, our study revealed that the immunomodulatory effect of the chemerin/CMKLR1 axis mediates innate immune evasion of S. aureus in vivo and likely increases susceptibility to S. aureus infection in obese individuals.
{"title":"The chemerin-CMKLR1 axis in keratinocytes impairs innate host defense against cutaneous Staphylococcus aureus infection","authors":"Yu Chen, Yan Song, Zhe Wang, Yangfan Lai, Wei Yin, Qian Cai, Miaomiao Han, Yiheng Cai, Yushan Xue, Zhengrong Chen, Xi Li, Jing Chen, Min Li, Huabin Li, Rui He","doi":"10.1038/s41423-024-01152-y","DOIUrl":"10.1038/s41423-024-01152-y","url":null,"abstract":"The skin is the most common site of Staphylococcus aureus infection, which can lead to various diseases, including invasive and life-threatening infections, through evasion of host defense. However, little is known about the host factors that facilitate the innate immune evasion of S. aureus in the skin. Chemerin, which is abundantly expressed in the skin and can be activated by proteases derived from S. aureus, has both direct bacteria-killing activity and immunomodulatory effects via interactions with its receptor CMKLR1. Here, we demonstrate that a lack of the chemerin/CMKLR1 axis increases the neutrophil-mediated host defense against S. aureus in a mouse model of cutaneous infection, whereas chemerin overexpression, which mimics high levels of chemerin in obese individuals, exacerbates S. aureus cutaneous infection. Mechanistically, we identified keratinocytes that express CMKLR1 as the main target of chemerin to suppress S. aureus-induced IL-33 expression, leading to impaired skin neutrophilia and bacterial clearance. CMKLR1 signaling specifically inhibits IL-33 expression induced by cell wall components but not secreted proteins of S. aureus by inhibiting Akt activation in mouse keratinocytes. Thus, our study revealed that the immunomodulatory effect of the chemerin/CMKLR1 axis mediates innate immune evasion of S. aureus in vivo and likely increases susceptibility to S. aureus infection in obese individuals.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292909","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 : 2024-03-26DOI: 10.1038/s41423-024-01138-w
Dieter Kabelitz
{"title":"Novel insights into regulation of butyrophilin molecules: critical components of cancer immunosurveillance by γδ T cells","authors":"Dieter Kabelitz","doi":"10.1038/s41423-024-01138-w","DOIUrl":"10.1038/s41423-024-01138-w","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01138-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292908","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}
Pub Date : 2024-03-21DOI: 10.1038/s41423-024-01154-w
Dawei Zou, Xiaolong Zhang, Shuang Li, Xiang Xiao, Nancy M. Gonzalez, Laurie J. Minze, Xian C. Li, Wenhao Chen
{"title":"Aerobic glycolysis enables the effector differentiation potential of stem-like CD4+ T cells to combat cancer","authors":"Dawei Zou, Xiaolong Zhang, Shuang Li, Xiang Xiao, Nancy M. Gonzalez, Laurie J. Minze, Xian C. Li, Wenhao Chen","doi":"10.1038/s41423-024-01154-w","DOIUrl":"10.1038/s41423-024-01154-w","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183902","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 : 2024-03-19DOI: 10.1038/s41423-024-01151-z
K. D. James, J. E. Cowan
{"title":"Insm1: orchestrating cellular mimicry in the thymus medulla","authors":"K. D. James, J. E. Cowan","doi":"10.1038/s41423-024-01151-z","DOIUrl":"10.1038/s41423-024-01151-z","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140165753","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}
Acetaldehyde dehydrogenase 2 (ALDH2) mutations are commonly found in a subgroup of the Asian population. However, the role of ALDH2 in septic acute respiratory distress syndrome (ARDS) remains unknown. Here, we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS. Intriguingly, ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA (cfDNA) and myeloperoxidase (MPO)-DNA than ALDH2WT-ARDS patients. To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS, we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice. In clinically relevant mouse sepsis models, Aldh2-/- mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis, a specific process that releases neutrophil extracellular traps (NETs) from neutrophils. Furthermore, we discovered that NETosis strongly promoted endothelial destruction, accelerated vascular leakage, and exacerbated septic ARDS. At the molecular level, ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4 (PAD4) to inhibit NETosis, which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP. Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis. Together, our data reveal a novel ALDH2-based protective mechanism against septic ARDS, and the activation of ALDH2 may be an effective treatment strategy for sepsis.
{"title":"Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS","authors":"Changchang Xu, Lin Zhang, Shaoyu Xu, Zichen Wang, Qi Han, Ying Lv, Xingfang Wang, Xiangxin Zhang, Qingju Zhang, Ying Zhang, Simeng He, Qiuhuan Yuan, Yuan Bian, Chuanbao Li, Jiali Wang, Feng Xu, Yihai Cao, Jiaojiao Pang, Yuguo Chen","doi":"10.1038/s41423-024-01146-w","DOIUrl":"10.1038/s41423-024-01146-w","url":null,"abstract":"Acetaldehyde dehydrogenase 2 (ALDH2) mutations are commonly found in a subgroup of the Asian population. However, the role of ALDH2 in septic acute respiratory distress syndrome (ARDS) remains unknown. Here, we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS. Intriguingly, ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA (cfDNA) and myeloperoxidase (MPO)-DNA than ALDH2WT-ARDS patients. To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS, we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice. In clinically relevant mouse sepsis models, Aldh2-/- mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis, a specific process that releases neutrophil extracellular traps (NETs) from neutrophils. Furthermore, we discovered that NETosis strongly promoted endothelial destruction, accelerated vascular leakage, and exacerbated septic ARDS. At the molecular level, ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4 (PAD4) to inhibit NETosis, which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP. Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis. Together, our data reveal a novel ALDH2-based protective mechanism against septic ARDS, and the activation of ALDH2 may be an effective treatment strategy for sepsis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109527","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 : 2024-03-08DOI: 10.1038/s41423-024-01147-9
Zvi G. Fridlender, Zvi Granot
{"title":"Neutrophils in the tumor microenvironment – when a company becomes a crowd","authors":"Zvi G. Fridlender, Zvi Granot","doi":"10.1038/s41423-024-01147-9","DOIUrl":"10.1038/s41423-024-01147-9","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01147-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140064998","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}
Pub Date : 2024-03-08DOI: 10.1038/s41423-024-01140-2
Mohammed Al-Talib, Sandra Dimonte, Ian R. Humphreys
Mucosal surfaces that line the respiratory, gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment. Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses. Numerous pathogenic viruses, including herpesviruses and retroviruses, exploit this environment to establish chronic infection. Effector and regulatory T-cell populations, including effector and resident memory T cells, play instrumental roles in mediating the transition from acute to chronic infection, where a degree of viral replication is tolerated to minimize immunopathology. Persistent antigen exposure during chronic viral infection leads to the evolution and divergence of these responses. In this review, we discuss advances in the understanding of mucosal T-cell immunity during chronic viral infections and how features of T-cell responses develop in different chronic viral infections of the mucosa. We consider how insights into T-cell immunity at mucosal surfaces could inform vaccine strategies: not only to protect hosts from chronic viral infections but also to exploit viruses that can persist within mucosal surfaces as vaccine vectors.
呼吸道、胃肠道和泌尿生殖道的粘膜表面是免疫系统与环境之间的主要界面。其独特的免疫学特征是，必须在对共生微生物和其他无害接触的耐受性与对病毒等致病威胁的保护之间取得平衡。包括疱疹病毒和逆转录病毒在内的大量致病性病毒利用这种环境建立了慢性感染。效应T细胞和调节T细胞群，包括效应T细胞和驻留记忆T细胞，在介导急性感染向慢性感染的过渡中发挥着重要作用，在这一过程中，病毒复制在一定程度上是可以容忍的，以最大限度地减少免疫病理。慢性病毒感染期间持续的抗原暴露会导致这些反应的进化和分化。在这篇综述中，我们将讨论对慢性病毒感染期间粘膜 T 细胞免疫的认识进展，以及 T 细胞反应的特征是如何在粘膜的不同慢性病毒感染中发展的。我们认为对粘膜表面 T 细胞免疫的深入了解可为疫苗策略提供信息：不仅可以保护宿主免受慢性病毒感染，还可以利用可在粘膜表面持续存在的病毒作为疫苗载体。
{"title":"Mucosal T-cell responses to chronic viral infections: Implications for vaccine design","authors":"Mohammed Al-Talib, Sandra Dimonte, Ian R. Humphreys","doi":"10.1038/s41423-024-01140-2","DOIUrl":"10.1038/s41423-024-01140-2","url":null,"abstract":"Mucosal surfaces that line the respiratory, gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment. Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses. Numerous pathogenic viruses, including herpesviruses and retroviruses, exploit this environment to establish chronic infection. Effector and regulatory T-cell populations, including effector and resident memory T cells, play instrumental roles in mediating the transition from acute to chronic infection, where a degree of viral replication is tolerated to minimize immunopathology. Persistent antigen exposure during chronic viral infection leads to the evolution and divergence of these responses. In this review, we discuss advances in the understanding of mucosal T-cell immunity during chronic viral infections and how features of T-cell responses develop in different chronic viral infections of the mucosa. We consider how insights into T-cell immunity at mucosal surfaces could inform vaccine strategies: not only to protect hosts from chronic viral infections but also to exploit viruses that can persist within mucosal surfaces as vaccine vectors.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01140-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140064997","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}
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