Pub Date : 2023-07-03DOI: 10.1038/s41577-023-00897-3
Takeshi Inoue, Tomohiro Kurosaki
Recent advances in studies of immune memory in mice and humans have reinforced the concept that memory B cells play a critical role in protection against repeated infections, particularly from variant viruses. Hence, insights into the development of high-quality memory B cells that can generate broadly neutralizing antibodies that bind such variants are key for successful vaccine development. Here, we review the cellular and molecular mechanisms by which memory B cells are generated and how these processes shape the antibody diversity and breadth of memory B cells. Then, we discuss the mechanisms of memory B cell reactivation in the context of established immune memory; the contribution of antibody feedback to this process has now begun to be reappreciated. Memory B cells are critical for protection against repeated infections, particularly with viral variants, and understanding their function and development is key for successful vaccine development. This Review discusses the cellular and molecular mechanisms of memory B cell generation and reactivation and how these processes shape antibody diversity and breadth.
小鼠和人类免疫记忆研究的最新进展强化了这样一个概念，即记忆 B 细胞在防止反复感染，尤其是变异病毒感染方面发挥着关键作用。因此，深入了解能产生结合此类变异病毒的广谱中和抗体的高质量记忆 B 细胞的发育情况是成功开发疫苗的关键。在此，我们回顾了记忆 B 细胞产生的细胞和分子机制，以及这些过程如何塑造记忆 B 细胞的抗体多样性和广度。然后，我们将讨论在已建立的免疫记忆背景下记忆 B 细胞再激活的机制；抗体反馈对这一过程的贡献现在已开始被重新认识。
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Pub Date : 2023-07-03DOI: 10.1038/s41577-023-00913-6
Mireia Cruz De Los Santos, Andreas Lundqvist
A preprint by Vardam-Kaur et al. reports a role for the ATP transporter PANX1 in regulating effector and memory CD8+ T cells.
Vardam-Kaur 等人的预印本报告了 ATP 转运体 PANX1 在调节效应和记忆 CD8+ T 细胞中的作用。
{"title":"Pannexin 1 regulates CD8+ T cell function and memory formation","authors":"Mireia Cruz De Los Santos, Andreas Lundqvist","doi":"10.1038/s41577-023-00913-6","DOIUrl":"10.1038/s41577-023-00913-6","url":null,"abstract":"A preprint by Vardam-Kaur et al. reports a role for the ATP transporter PANX1 in regulating effector and memory CD8+ T cells.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"478-478"},"PeriodicalIF":100.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9985591","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 : 2023-07-03DOI: 10.1038/s41577-023-00902-9
Roland S. Liblau, Daniela Latorre, Birgitte R. Kornum, Yves Dauvilliers, Emmanuel J. Mignot
Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT; also known as orexin) peptides. An immune-mediated pathology for NT1 has long been suspected given its exceptionally tight association with the MHC class II allele HLA-DQB1*06:02, as well as recent genetic evidence showing associations with polymorphisms of T cell receptor genes and other immune-relevant loci and the increased incidence of NT1 that has been observed after vaccination with the influenza vaccine Pandemrix. The search for both self-antigens and foreign antigens recognized by the pathogenic T cell response in NT1 is ongoing. Increased T cell reactivity against HCRT has been consistently reported in patients with NT1, but data demonstrating a primary role for T cells in neuronal destruction are currently lacking. Animal models are providing clues regarding the roles of autoreactive CD4+ and CD8+ T cells in the disease. Elucidation of the pathogenesis of NT1 will allow for the development of targeted immunotherapies at disease onset and could serve as a model for other immune-mediated neurological diseases. This article reviews growing evidence suggesting that narcolepsy, a chronic sleep disorder caused by deficiency of hypocretin (also known as orexin), has an immune-mediated basis, explores the potential role of autoreactive lymphocytes in the disease process, and proposes future research directions to elucidate its pathogenesis.
1 型嗜睡症（NT1）是一种慢性睡眠障碍，是由于一小部分下丘脑神经元缺失导致的，这些神经元能产生促进唤醒的视网膜下视素（HCRT，又称奥曲肽肽）。鉴于 NT1 与 MHC II 类等位基因 HLA-DQB1*06:02 的紧密联系，以及最近的遗传学证据显示与 T 细胞受体基因的多态性和其他免疫相关位点的联系，以及在接种流感疫苗 Pandemrix 后观察到的 NT1 发病率的增加，人们长期以来一直怀疑 NT1 是一种免疫介导的病理现象。目前正在寻找 NT1 致病性 T 细胞反应所识别的自身抗原和外来抗原。不断有报告称，NT1 患者的 T 细胞对 HCRT 的反应性增高，但目前还缺乏证明 T 细胞在神经元破坏中起主要作用的数据。动物模型为自反应性 CD4+ 和 CD8+ T 细胞在疾病中的作用提供了线索。阐明 NT1 的发病机理将有助于在发病初期开发有针对性的免疫疗法，并可作为其他免疫介导的神经系统疾病的模型。
{"title":"The immunopathogenesis of narcolepsy type 1","authors":"Roland S. Liblau, Daniela Latorre, Birgitte R. Kornum, Yves Dauvilliers, Emmanuel J. Mignot","doi":"10.1038/s41577-023-00902-9","DOIUrl":"10.1038/s41577-023-00902-9","url":null,"abstract":"Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT; also known as orexin) peptides. An immune-mediated pathology for NT1 has long been suspected given its exceptionally tight association with the MHC class II allele HLA-DQB1*06:02, as well as recent genetic evidence showing associations with polymorphisms of T cell receptor genes and other immune-relevant loci and the increased incidence of NT1 that has been observed after vaccination with the influenza vaccine Pandemrix. The search for both self-antigens and foreign antigens recognized by the pathogenic T cell response in NT1 is ongoing. Increased T cell reactivity against HCRT has been consistently reported in patients with NT1, but data demonstrating a primary role for T cells in neuronal destruction are currently lacking. Animal models are providing clues regarding the roles of autoreactive CD4+ and CD8+ T cells in the disease. Elucidation of the pathogenesis of NT1 will allow for the development of targeted immunotherapies at disease onset and could serve as a model for other immune-mediated neurological diseases. This article reviews growing evidence suggesting that narcolepsy, a chronic sleep disorder caused by deficiency of hypocretin (also known as orexin), has an immune-mediated basis, explores the potential role of autoreactive lymphocytes in the disease process, and proposes future research directions to elucidate its pathogenesis.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"24 1","pages":"33-48"},"PeriodicalIF":100.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749636","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 : 2023-06-29DOI: 10.1038/s41577-023-00910-9
Yavuz F. Yazicioglu, Alexander J. Clarke
A preprint by Nakandakari-Higa et al. introduces universal LIPSTIC (uLIPSTIC), a labelling technique for the detection of physical interactions between any cell types without the requirement for specific receptor–ligand interaction.
{"title":"The kiss a cell can’t forget: tracking cell–cell interactions with uLIPSTIC","authors":"Yavuz F. Yazicioglu, Alexander J. Clarke","doi":"10.1038/s41577-023-00910-9","DOIUrl":"10.1038/s41577-023-00910-9","url":null,"abstract":"A preprint by Nakandakari-Higa et al. introduces universal LIPSTIC (uLIPSTIC), a labelling technique for the detection of physical interactions between any cell types without the requirement for specific receptor–ligand interaction.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"477-477"},"PeriodicalIF":100.3,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9920476","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 : 2023-06-28DOI: 10.1038/s41577-023-00912-7
Christa Haase
In this Tools of the Trade article, Christa Haase (at the Charles Lin lab) describes a technique called Image-seq that enables image-guided cell isolation from a specific, intact tissue location for subsequent single-cell gene expression analysis.
在这篇《贸易工具》（Tools of the Trade）文章中，Christa Haase（查尔斯-林实验室）介绍了一种名为 "图像-序列"（Image-seq）的技术，该技术可在图像引导下从特定的完整组织位置分离细胞，以便随后进行单细胞基因表达分析。
{"title":"Image-seq: image-guided cell isolation for spatially resolved transcriptomic analysis","authors":"Christa Haase","doi":"10.1038/s41577-023-00912-7","DOIUrl":"10.1038/s41577-023-00912-7","url":null,"abstract":"In this Tools of the Trade article, Christa Haase (at the Charles Lin lab) describes a technique called Image-seq that enables image-guided cell isolation from a specific, intact tissue location for subsequent single-cell gene expression analysis.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"473-473"},"PeriodicalIF":100.3,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10281273","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 : 2023-06-27DOI: 10.1038/s41577-023-00909-2
Anthony Altieri, Matthew B. Buechler
A preprint by Sbierski-Kind et al. shows that IL-33-producing adventitial fibroblasts provide a stromal niche for ILC2s that limits IL-17-mediated liver fibrosis.
{"title":"Adventitial fibroblast–ILC2 niche restrains liver fibrosis","authors":"Anthony Altieri, Matthew B. Buechler","doi":"10.1038/s41577-023-00909-2","DOIUrl":"10.1038/s41577-023-00909-2","url":null,"abstract":"A preprint by Sbierski-Kind et al. shows that IL-33-producing adventitial fibroblasts provide a stromal niche for ILC2s that limits IL-17-mediated liver fibrosis.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"477-477"},"PeriodicalIF":100.3,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9950705","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 : 2023-06-21DOI: 10.1038/s41577-023-00908-3
Xiaoyun Dai
In this Tools of the Trade article, Xiaoyun Dai (of the Sidi Chen lab) developed a CRISPR-based platform termed CLASH to generate a large pool of precisely gene-modified CAR T cells, from which the most desirable variants could be selected.
在这篇 "贸易工具 "文章中，戴小云（Sidi Chen 实验室）开发了一个基于 CRISPR 的平台，称为 CLASH，用于生成大量经过精确基因修饰的 CAR T 细胞，并从中筛选出最理想的变体。
{"title":"CLASH: large-scale engineering system for the discovery of better CAR T cells","authors":"Xiaoyun Dai","doi":"10.1038/s41577-023-00908-3","DOIUrl":"10.1038/s41577-023-00908-3","url":null,"abstract":"In this Tools of the Trade article, Xiaoyun Dai (of the Sidi Chen lab) developed a CRISPR-based platform termed CLASH to generate a large pool of precisely gene-modified CAR T cells, from which the most desirable variants could be selected.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 9","pages":"541-541"},"PeriodicalIF":100.3,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10432818","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 : 2023-06-19DOI: 10.1038/s41577-023-00893-7
Jorge L. Trujillo-Ochoa, Majid Kazemian, Behdad Afzali
Forkhead box protein 3-expressing (FOXP3+) regulatory T cells (Treg cells) suppress conventional T cells and are essential for immunological tolerance. FOXP3, the master transcription factor of Treg cells, controls the expression of multiples genes to guide Treg cell differentiation and function. However, only a small fraction (<10%) of Treg cell-associated genes are directly bound by FOXP3, and FOXP3 alone is insufficient to fully specify the Treg cell programme, indicating a role for other accessory transcription factors operating upstream, downstream and/or concurrently with FOXP3 to direct Treg cell specification and specialized functions. Indeed, the heterogeneity of Treg cells can be at least partially attributed to differential expression of transcription factors that fine-tune their trafficking, survival and functional properties, some of which are niche-specific. In this Review, we discuss the emerging roles of accessory transcription factors in controlling Treg cell identity. We specifically focus on members of the basic helix–loop–helix family (AHR), basic leucine zipper family (BACH2, NFIL3 and BATF), CUT homeobox family (SATB1), zinc-finger domain family (BLIMP1, Ikaros and BCL-11B) and interferon regulatory factor family (IRF4), as well as lineage-defining transcription factors (T-bet, GATA3, RORγt and BCL-6). Understanding the imprinting of Treg cell identity and specialized function will be key to unravelling basic mechanisms of autoimmunity and identifying novel targets for drug development. Regulatory T cells (Treg cells) are controlled by a raft of transcription factors besides Forkhead box protein 3 (FOXP3). As detailed in this Review, these accessory transcription factors act alone or together with FOXP3 to coordinate Treg cell specification and function, and account for heterogeneity of niche-specific Treg cells.
{"title":"The role of transcription factors in shaping regulatory T cell identity","authors":"Jorge L. Trujillo-Ochoa, Majid Kazemian, Behdad Afzali","doi":"10.1038/s41577-023-00893-7","DOIUrl":"10.1038/s41577-023-00893-7","url":null,"abstract":"Forkhead box protein 3-expressing (FOXP3+) regulatory T cells (Treg cells) suppress conventional T cells and are essential for immunological tolerance. FOXP3, the master transcription factor of Treg cells, controls the expression of multiples genes to guide Treg cell differentiation and function. However, only a small fraction (<10%) of Treg cell-associated genes are directly bound by FOXP3, and FOXP3 alone is insufficient to fully specify the Treg cell programme, indicating a role for other accessory transcription factors operating upstream, downstream and/or concurrently with FOXP3 to direct Treg cell specification and specialized functions. Indeed, the heterogeneity of Treg cells can be at least partially attributed to differential expression of transcription factors that fine-tune their trafficking, survival and functional properties, some of which are niche-specific. In this Review, we discuss the emerging roles of accessory transcription factors in controlling Treg cell identity. We specifically focus on members of the basic helix–loop–helix family (AHR), basic leucine zipper family (BACH2, NFIL3 and BATF), CUT homeobox family (SATB1), zinc-finger domain family (BLIMP1, Ikaros and BCL-11B) and interferon regulatory factor family (IRF4), as well as lineage-defining transcription factors (T-bet, GATA3, RORγt and BCL-6). Understanding the imprinting of Treg cell identity and specialized function will be key to unravelling basic mechanisms of autoimmunity and identifying novel targets for drug development. Regulatory T cells (Treg cells) are controlled by a raft of transcription factors besides Forkhead box protein 3 (FOXP3). As detailed in this Review, these accessory transcription factors act alone or together with FOXP3 to coordinate Treg cell specification and function, and account for heterogeneity of niche-specific Treg cells.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 12","pages":"842-856"},"PeriodicalIF":100.3,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9664256","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 : 2023-06-15DOI: 10.1038/s41577-023-00894-6
Daolin Tang, Rui Kang, Herbert J. Zeh, Michael T. Lotze
Fifty years since the initial discovery of HMGB1 in 1973 as a structural protein of chromatin, HMGB1 is now known to regulate diverse biological processes depending on its subcellular or extracellular localization. These functions include promoting DNA damage repair in the nucleus, sensing nucleic acids and inducing innate immune responses and autophagy in the cytosol and binding protein partners in the extracellular environment and stimulating immunoreceptors. In addition, HMGB1 is a broad sensor of cellular stress that balances cell death and survival responses essential for cellular homeostasis and tissue maintenance. HMGB1 is also an important mediator secreted by immune cells that is involved in a range of pathological conditions, including infectious diseases, ischaemia–reperfusion injury, autoimmunity, cardiovascular and neurodegenerative diseases, metabolic disorders and cancer. In this Review, we discuss the signalling mechanisms, cellular functions and clinical relevance of HMGB1 and describe strategies to modify its release and biological activities in the setting of various diseases. Fifty years since the discovery of HMGB1 protein, its physiological and pathological roles have been extensively studied. This Review covers the structure, localization and functions of HMGB1 in immune responses, including historical foundations and recent advances.
{"title":"The multifunctional protein HMGB1: 50 years of discovery","authors":"Daolin Tang, Rui Kang, Herbert J. Zeh, Michael T. Lotze","doi":"10.1038/s41577-023-00894-6","DOIUrl":"10.1038/s41577-023-00894-6","url":null,"abstract":"Fifty years since the initial discovery of HMGB1 in 1973 as a structural protein of chromatin, HMGB1 is now known to regulate diverse biological processes depending on its subcellular or extracellular localization. These functions include promoting DNA damage repair in the nucleus, sensing nucleic acids and inducing innate immune responses and autophagy in the cytosol and binding protein partners in the extracellular environment and stimulating immunoreceptors. In addition, HMGB1 is a broad sensor of cellular stress that balances cell death and survival responses essential for cellular homeostasis and tissue maintenance. HMGB1 is also an important mediator secreted by immune cells that is involved in a range of pathological conditions, including infectious diseases, ischaemia–reperfusion injury, autoimmunity, cardiovascular and neurodegenerative diseases, metabolic disorders and cancer. In this Review, we discuss the signalling mechanisms, cellular functions and clinical relevance of HMGB1 and describe strategies to modify its release and biological activities in the setting of various diseases. Fifty years since the discovery of HMGB1 protein, its physiological and pathological roles have been extensively studied. This Review covers the structure, localization and functions of HMGB1 in immune responses, including historical foundations and recent advances.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 12","pages":"824-841"},"PeriodicalIF":100.3,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012075","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 : 2023-06-15DOI: 10.1038/s41577-023-00905-6
Kirsty Minton
Gillian Griffiths and colleagues show that T cell receptor downregulation at the immune synapse occurs through ectocytosis, which terminates receptor signalling and promotes dissociation from target cells.
{"title":"Serial killing enabled by T cell receptor ectocytosis","authors":"Kirsty Minton","doi":"10.1038/s41577-023-00905-6","DOIUrl":"10.1038/s41577-023-00905-6","url":null,"abstract":"Gillian Griffiths and colleagues show that T cell receptor downregulation at the immune synapse occurs through ectocytosis, which terminates receptor signalling and promotes dissociation from target cells.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"475-475"},"PeriodicalIF":100.3,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9920436","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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