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New insights into the ontogeny, diversity, maturation and survival of long-lived plasma cells 对长寿命浆细胞的发生、多样性、成熟和存活的新认识。
IF 67.7 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-02-08 DOI: 10.1038/s41577-024-00991-0
David R. Fooksman, Zhixin Jing, Rosa Park
Plasma cells are unique immune effectors, capable of producing large amounts of high-affinity antibodies that protect against pathogenic infections. Although most plasma cells have short lifespans, certain conditions or vaccinations can give rise to long-lived plasma cells (LLPCs) that provide individuals with lifelong protection against pathogen exposure. The nature of these LLPCs is poorly understood; however, recent studies have shed new light on the ontogeny, diversity, maturation and survival of these unique cells. Whereas LLPCs had been thought to arise preferentially from germinal centres, novel genetic tools have revealed that they can originate from various stages throughout the humoral response. Furthermore, new single-cell analyses have shown that mouse and human plasma cells are heterogeneous and may undergo further maturation in situ in the bone marrow niche. Finally, plasma cells were previously considered to be sessile cells maintained in fixed survival niches, but new data show that plasma cell subsets can differentially migrate and organize into clusters that may be associated with survival niches. These descriptive findings provide new insights into how cell-intrinsic programmes and extrinsic factors may regulate the longevity of plasma cells in various contexts, which suggest new research avenues for their functional validation. In this Progress article, Fooksman and colleagues review recent advances in the study of long-lived plasma cells, using genetic labelling tools, RNA sequencing and in vivo imaging to characterize the differentiation and survival of this rare cell type in mice and humans.
浆细胞是一种独特的免疫效应器,能够产生大量高亲和力抗体,抵御病原体感染。虽然大多数浆细胞的寿命都很短,但在某些情况下或接种疫苗后会产生长寿命浆细胞(LLPCs),为个体提供终生保护,使其免受病原体感染。人们对这些长寿命浆细胞的性质知之甚少;不过,最近的研究对这些独特细胞的本体、多样性、成熟和存活有了新的认识。过去人们认为 LLPCs 优先产生于生殖中心,而新的基因工具揭示了它们可以产生于整个体液反应的不同阶段。此外,新的单细胞分析表明,小鼠和人类浆细胞具有异质性,可能在骨髓龛原位进一步成熟。最后,浆细胞以前被认为是维持在固定生存龛中的无柄细胞,但新的数据显示,浆细胞亚群可以以不同方式迁移并组织成可能与生存龛相关的集群。这些描述性发现为细胞内在程序和外在因素如何在各种情况下调节浆细胞的寿命提供了新的见解,为其功能验证提供了新的研究途径。
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引用次数: 0
The immunology of type 1 diabetes 1 型糖尿病的免疫学
IF 100.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-02-02 DOI: 10.1038/s41577-023-00985-4
Kevan C. Herold, Thomas Delong, Ana Luisa Perdigoto, Noah Biru, Todd M. Brusko, Lucy S. K. Walker
Following the seminal discovery of insulin a century ago, treatment of individuals with type 1 diabetes (T1D) has been largely restricted to efforts to monitor and treat metabolic glucose dysregulation. The recent regulatory approval of the first immunotherapy that targets T cells as a means to delay the autoimmune destruction of pancreatic β-cells highlights the critical role of the immune system in disease pathogenesis and tends to pave the way for other immune-targeted interventions for T1D. Improving the efficacy of such interventions across the natural history of the disease will probably require a more detailed understanding of the immunobiology of T1D, as well as technologies to monitor residual β-cell mass and function. Here we provide an overview of the immune mechanisms that underpin the pathogenesis of T1D, with a particular emphasis on T cells. The first immune-targeted drug for type 1 diabetes (T1D), teplizumab, received regulatory approval by the US FDA in 2022. In this Review, Herold, Walker and colleagues examine the immune mechanisms that underpin T1D and provide an overview of immune-targeted strategies for T1D that are currently in development.
自一个世纪前胰岛素的重大发现以来,对1型糖尿病(T1D)患者的治疗主要局限于监测和治疗代谢性葡萄糖失调。最近,首个以 T 细胞为靶点的免疫疗法获得了监管部门的批准,该疗法可延缓胰腺 β 细胞的自身免疫破坏,这凸显了免疫系统在疾病发病机制中的关键作用,并有望为其他以免疫为靶点的 T1D 干预疗法铺平道路。要提高此类干预措施在疾病自然史中的疗效,可能需要更详细地了解 T1D 的免疫生物学,以及监测残余 β 细胞数量和功能的技术。在此,我们概述了支撑 T1D 发病机制的免疫机制,并特别强调了 T 细胞。
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引用次数: 0
Neutrophil surface RNAs promote entry to inflamed sites 中性粒细胞表面 RNA 促进进入发炎部位
IF 100.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-02-01 DOI: 10.1038/s41577-024-01000-0
Kirsty Minton
Glycosylated RNAs on the surface of neutrophils bind P-selectin on endothelial cells to mediate recruitment to sites of inflammation.
中性粒细胞表面的糖基化 RNA 与内皮细胞上的 P-选择素结合,介导中性粒细胞被招募到炎症部位。
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引用次数: 0
Author Correction: The effect of physical exercise on anticancer immunity 作者更正:体育锻炼对抗癌免疫力的影响。
IF 100.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-02-01 DOI: 10.1038/s41577-024-00999-6
Carmen Fiuza-Luces, Pedro L. Valenzuela, Beatriz G. Gálvez, Manuel Ramírez, Alejandro López-Soto, Richard J. Simpson, Alejandro Lucia
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引用次数: 0
Age-related motor deficits caused by clonal haematopoiesis-driven, monocyte-derived microglia 由克隆造血驱动的单核细胞衍生小胶质细胞导致的与年龄相关的运动障碍
IF 100.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-01-30 DOI: 10.1038/s41577-024-00997-8
Austeja Baleviciute, Lily Keane
A preprint by Kim et al. shows that the brain parenchyma can be seeded with age with clonal haematopoiesis-derived monocytes that drive neuropathology.
Kim 等人的预印本显示,随着年龄的增长,脑实质中会出现克隆性造血单核细胞,从而引发神经病理学。
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引用次数: 0
New immune cell engagers for cancer immunotherapy 用于癌症免疫疗法的新型免疫细胞诱导剂。
IF 67.7 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-01-25 DOI: 10.1038/s41577-023-00982-7
Aurore Fenis, Olivier Demaria, Laurent Gauthier, Eric Vivier, Emilie Narni-Mancinelli
There have been major advances in the immunotherapy of cancer in recent years, including the development of T cell engagers — antibodies engineered to redirect T cells to recognize and kill cancer cells — for the treatment of haematological malignancies. However, the field still faces several challenges to develop agents that are consistently effective in a majority of patients and cancer types, such as optimizing drug dose, overcoming treatment resistance and improving efficacy in solid tumours. A new generation of T cell-targeted molecules was developed to tackle these issues that are potentially more effective and safer. In addition, agents designed to engage the antitumour activities of other immune cells, including natural killer cells and myeloid cells, are showing promise and have the potential to treat a broader range of cancers. Immune cell engagers — antibody-based molecules engineered to direct immune effector cells to recognize and kill cancer cells — represent a rapidly expanding approach in cancer therapy. Here, the authors bring us up to date with the targets, challenges and opportunities for harnessing the anticancer activities of T cells, natural killer cells and myeloid cells with immune cell engagers.
近年来,癌症免疫疗法取得了重大进展,包括开发出治疗血液系统恶性肿瘤的 T 细胞吞噬剂(T 细胞吞噬剂是一种抗体,可引导 T 细胞识别并杀死癌细胞)。然而,要开发出对大多数患者和癌症类型持续有效的药物,该领域仍面临一些挑战,如优化药物剂量、克服耐药性和提高实体瘤的疗效。新一代 T 细胞靶向分子的开发就是为了解决这些问题,它们可能更有效、更安全。此外,旨在调动其他免疫细胞(包括自然杀伤细胞和类髓鞘细胞)抗肿瘤活性的药物也显示出良好的前景,有望治疗更广泛的癌症。
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引用次数: 0
Using BCG vaccination to protect against COVID-19: when reality fails to meet expectation 使用卡介苗预防 COVID-19:当现实与期望不符时。
IF 100.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-01-18 DOI: 10.1038/s41577-024-00992-z
Laure F. Pittet, Christie C. A. Noble, Nicole L. Messina, Nigel Curtis
While anticipating the development of a COVID-19-specific vaccine, several randomized controlled trials (RCTs) explored the potential of BCG vaccination to protect against COVID-19, based on trials demonstrating beneficial effects of BCG vaccination on unrelated infections and all-cause mortality in neonates in high-mortality geographical settings. Results are now available from 12 RCTs, which suggest that BCG vaccination is not an effective intervention against COVID-19. That the BCG–COVID-19 trials failed to meet expectation emphasizes the importance of rigorous clinical trials to validate hypotheses, even in urgent situations such as a pandemic.
在期待开发 COVID-19 特异性疫苗的同时,几项随机对照试验 (RCT) 探索了接种卡介苗预防 COVID-19 的可能性,这些试验基于卡介苗接种对高死亡率地区新生儿的非相关感染和全因死亡率的有益影响。目前已有 12 项研究性试验的结果表明,接种卡介苗并不是预防 COVID-19 的有效干预措施。卡介苗-COVID-19试验未能达到预期效果,这强调了严格的临床试验对验证假设的重要性,即使在大流行等紧急情况下也是如此。
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引用次数: 0
Novel insights into the immune response to bacterial T cell superantigens 细菌 T 细胞超级抗原免疫反应的新见解
IF 100.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-01-15 DOI: 10.1038/s41577-023-00979-2
Stephen W. Tuffs, Karine Dufresne, Aanchal Rishi, Nicholas R. Walton, John K. McCormick
Bacterial T cell superantigens (SAgs) are a family of microbial exotoxins that function to activate large numbers of T cells simultaneously. SAgs activate T cells by direct binding and crosslinking of the lateral regions of MHC class II molecules on antigen-presenting cells with T cell receptors (TCRs) on T cells; these interactions alter the normal TCR–peptide–MHC class II architecture to activate T cells in a manner that is independent of the antigen specificity of the TCR. SAgs have well-recognized, central roles in human diseases such as toxic shock syndrome and scarlet fever through their quantitative effects on the T cell response; in addition, numerous other consequences of SAg-driven T cell activation are now being recognized, including direct roles in the pathogenesis of endocarditis, bloodstream infections, skin disease and pharyngitis. In this Review, we summarize the expanding family of bacterial SAgs and how these toxins can engage highly diverse adaptive immune receptors. We highlight recent findings regarding how SAg-driven manipulation of the adaptive immune response may operate in multiple human diseases, as well as contributing to the biology and life cycle of SAg-producing bacterial pathogens. This Review provides an updated assessment of the expanding family of T cell-activating bacterial superantigens, emphasizing potential roles of these toxins in various disease states as well as their contribution to the evolution of the bacterial pathogens Staphylococcus aureus and Streptococcus pyogenes.
细菌 T 细胞超抗原(SAgs)是微生物外毒素的一个家族,具有同时激活大量 T 细胞的功能。SAgs 通过抗原递呈细胞上 MHC II 类分子的横向区域与 T 细胞上的 T 细胞受体(TCR)直接结合和交联来激活 T 细胞;这些相互作用改变了正常的 TCR 肽-MHC II 类结构,从而以一种独立于 TCR 抗原特异性的方式激活 T 细胞。通过对 T 细胞反应的定量影响,SAgs 在中毒性休克综合症和猩红热等人类疾病中发挥着公认的核心作用;此外,SAg 驱动的 T 细胞活化还产生了许多其他后果,包括在心内膜炎、血流感染、皮肤病和咽炎的发病机制中发挥直接作用。在这篇综述中,我们总结了不断扩大的细菌 SAg 家族,以及这些毒素如何与高度多样化的适应性免疫受体发生作用。我们重点介绍了最近的研究发现,即由 SAg 驱动的适应性免疫反应是如何在多种人类疾病中发挥作用的,以及对产生 SAg 的细菌病原体的生物学和生命周期的影响。
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引用次数: 0
Blood neutrophil subset predicts the success of immune checkpoint inhibitors in cancer 血液中性粒细胞亚群可预测免疫检查点抑制剂治疗癌症的成功率
IF 100.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-01-15 DOI: 10.1038/s41577-024-00993-y
Yvonne Bordon
A population of interferon-stimulated neutrophils can predict the success of immunotherapy outcomes in various cancers.
干扰素刺激的中性粒细胞群可以预测各种癌症的免疫疗法是否成功。
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引用次数: 0
Alternative RNA splicing generates shared clonal neoantigens across different types of cancer 交替 RNA 剪接产生不同类型癌症的共享克隆新抗原
IF 100.3 1区 医学 Q1 Immunology and Microbiology Pub Date : 2024-01-12 DOI: 10.1038/s41577-023-00986-3
Matthew Brown, Nicolas Vabret
A preprint by Kwok et al. describes the identification of common neojunction-derived antigens that could serve as targets for ‘off the shelf’ vaccines or adoptive cell therapies for patients with various types of cancer.
Kwok 等人的一篇预发表论文描述了常见的新结合源抗原的鉴定,这些抗原可作为 "现成 "疫苗或采用细胞疗法的靶点,用于治疗各种类型的癌症患者。
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引用次数: 0
期刊
Nature Reviews Immunology
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