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The tissue glycome as regulator of immune activation and tolerance mediated by C-type lectins and Siglecs 由 C 型凝集素和 Siglecs 介导的组织糖蛋白是免疫激活和耐受的调节器
IF 7.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.smim.2024.101913
Eleonora Nardini , Ernesto Rodriguez , Yvette van Kooyk
The immune system is a complex network of highly specialized microenvironments, denominated niches, which arise from dynamic interactions between immune and parenchymal cells as well as acellular components such as structural elements and local molecular signals. A critical, yet underexplored, layer shaping these niches is the glycome, the complete repertoire of glycans and glycoconjugates produced by cells. The glycome is prevalent in the outer membrane of cells and their secreted components, and can be sensed by glycan binding receptors on immune cells. These receptors detect changes in glycosylation and consequently modulate immune cell activity, trafficking, and signalling, altering homeostasis. Tissues like the brain and the placenta are prone to accommodate tolerance, while the gut and the thymus are sensitive to inflammation. We provide here an overview of current literature that shows the impact of altered glycosylation of tissues on host immune cells and how interference in this process may lead to new diagnostics and immune therapeutics, aiming to restore the immune balance in autoimmunity and cancer.
免疫系统是一个由高度特化的微环境组成的复杂网络,这些微环境被称为 "龛"。"龛 "是由免疫细胞和实质细胞以及结构元素和局部分子信号等细胞成分之间的动态相互作用产生的。形成这些龛位的一个关键但尚未被充分探索的层次是糖体(glycome),即细胞产生的全部聚糖和聚糖共轭物。糖集普遍存在于细胞外膜及其分泌成分中,并能被免疫细胞上的糖结合受体感知。这些受体能检测糖基化的变化,从而调节免疫细胞的活动、贩运和信号传递,改变体内平衡。大脑和胎盘等组织容易产生耐受性,而肠道和胸腺则对炎症敏感。我们在此概述了目前的文献,这些文献显示了组织糖基化改变对宿主免疫细胞的影响,以及干扰这一过程如何可能导致新的诊断和免疫疗法,从而恢复自身免疫和癌症的免疫平衡。
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引用次数: 0
Galectins and Host–Pathogen Interactions: The roles in viral infections Galectins 和宿主-病原体相互作用:在病毒感染中的作用
IF 7.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.smim.2024.101911
Sheng-Fang Wang , Hung-Lin Chen , Fu-Tong Liu
Galectins, a family of carbohydrate-binding proteins, play crucial roles in the host–virus interaction landscape. This review explores the multifaceted contributions of endogenous galectins to various stages of the viral lifecycle, including attachment, replication, assembly, and release of progeny virions. Recent studies have indicated that viral infections can induce the expression and secretion of specific galectins, with elucidated signaling pathways in some cases, enhancing our understanding of their regulatory mechanisms. While many studies have focused on the effects of exogenous recombinant galectins, there is growing interest in the intrinsic functions of endogenous galectins, particularly through genetic alterations in cellular models. This review highlights the need for further research to uncover the complex roles of galectins in modulating viral infections and emphasizes their potential as therapeutic targets in the fight against viral diseases. Understanding these interactions could pave the way for novel strategies to enhance host defense mechanisms and mitigate viral pathogenesis.
Galectins 是碳水化合物结合蛋白的一个家族,在宿主与病毒的相互作用中发挥着至关重要的作用。本综述探讨了内源性半整联蛋白对病毒生命周期各个阶段的多方面贡献,包括附着、复制、组装和释放后代病毒。最近的研究表明,病毒感染可诱导特定半凝集素的表达和分泌,有些研究还阐明了信号通路,从而加深了我们对其调控机制的了解。虽然许多研究都集中在外源性重组半整联蛋白的作用上,但人们对内源性半整联蛋白内在功能的兴趣也与日俱增,特别是通过细胞模型中的基因改变。这篇综述强调了进一步研究的必要性,以揭示半整联蛋白在调节病毒感染中的复杂作用,并强调了它们在抗击病毒性疾病中作为治疗靶点的潜力。了解这些相互作用可为采取新策略增强宿主防御机制和减轻病毒致病机理铺平道路。
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引用次数: 0
ABO blood groups and galectins: Implications in transfusion medicine and innate immunity ABO 血型和半凝血酶:输血医学和先天免疫的意义
IF 7.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.smim.2024.101892
Connie M. Arthur , Marie Hollenhorst , Shang-Chuen Wu , Ryan Jajosky , Hirotomo Nakahara , Hau-Ming Jan , Leon Zheng , Mischa Covington , Seth Rakoff-Nahoum , Melissa Yeung , William Lane , Cassandra Josephson , Richard D. Cummings , Sean R. Stowell
ABO blood group antigens, which are complex carbohydrate moieties, and the first human polymorphisms identified, are critical in transfusion medicine and transplantation. Despite their discovery over a century ago, significant questions remain about the development of anti-ABO antibodies and the structural features of ABO antigens that cause hemolytic transfusion reactions. Anti-ABO antibodies develop naturally during the first few months of life, in contrast to other red blood cell (RBC) alloantibodies which form after allogeneic RBC exposure. Anti-ABO antibodies are the most common immune barrier to transfusion and transplantation, but the factors driving their formation are incompletely understood. Some studies suggest that microbes that express glycans similar in structure to the blood group antigens could play a role in anti-blood group antibody formation. While the role of these microbes in clinically relevant anti-blood group antibody formation remains to be defined, the presence of these microbes raises questions about how blood group-positive individuals protect themselves against blood group molecular mimicry. Recent studies suggest that galectins can bind and kill microbes that mimic blood group antigens, suggesting a unique host defense mechanism against microbial molecular mimicry. However, new models are needed to fully define the impact of microbes, galectins, or other factors on the development of clinically relevant naturally occurring anti-blood group antibodies.
ABO 血型抗原是一种复杂的碳水化合物分子,也是最早发现的人类多态性,在输血医学和移植中至关重要。尽管抗 ABO 抗体在一个多世纪前就已被发现,但关于抗 ABO 抗体的产生以及导致溶血性输血反应的 ABO 抗原结构特征的重大问题依然存在。抗ABO抗体是在婴儿出生后的头几个月自然产生的,而其他红细胞(RBC)异体抗体则是在接触异体RBC后形成的。抗逆转录病毒抗体是输血和移植最常见的免疫屏障,但其形成的驱动因素尚不完全清楚。一些研究表明,表达与血型抗原结构相似的聚糖的微生物可能在抗血型抗体的形成中发挥作用。虽然这些微生物在临床相关的抗血型抗体形成中的作用仍有待确定,但这些微生物的存在提出了血型阳性者如何保护自己免受血型分子模仿的问题。最近的研究表明,半凝集素能结合并杀死模仿血型抗原的微生物,这表明宿主有一种独特的防御机制来抵御微生物的分子模仿。然而,要全面确定微生物、半凝集素或其他因素对临床相关的自然产生的抗血型抗体的影响,还需要新的模型。
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引用次数: 0
NGS data analysis for molecular diagnosis of Inborn Errors of Immunity 用于先天性免疫错误分子诊断的 NGS 数据分析
IF 7.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.smim.2024.101901
XT Yang, WL Yang, YL Lau
Inborn errors of immunity (IEI) encompass a group of disorders with a strong genetic component. Prompt and accurate diagnosis of these disorders is essential for effective clinical management. Next-generation sequencing (NGS) has significantly enhanced the diagnostic process by offering a comprehensive and scalable approach for identifying genomic variations causal for these disorders. Nevertheless, the bioinformatics analysis of NGS data poses several challenges. In this review, we explore these challenges and share our insights on addressing them, aiming to improve the overall diagnostic yield.
先天性免疫错误(IEI)包括一组遗传因素很强的疾病。及时准确地诊断这些疾病对有效的临床治疗至关重要。下一代测序(NGS)提供了一种全面、可扩展的方法来识别导致这些疾病的基因组变异,从而极大地改进了诊断过程。然而,NGS 数据的生物信息学分析带来了一些挑战。在这篇综述中,我们将探讨这些挑战,并分享我们应对这些挑战的见解,以提高整体诊断率。
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引用次数: 0
Sialic acid and Siglec receptors in tumor immunity and immunotherapy 肿瘤免疫和免疫疗法中的 Sialic acid 和 Siglec 受体。
IF 7.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.smim.2024.101893
Natalia Rodrigues Mantuano , Heinz Läubli
Immunotherapy, including immune checkpoint inhibition, has transformed cancer therapy in recent years, providing new and potentially curative options for patients with even advanced disease. However, only a minority of patients achieve long-lasting remissions, and resistance to immune checkpoint inhibition is common. Recently, the sialic acid-Siglec axis has been proposed as a new immune checkpoint that could overcome resistance to current immunotherapy options. In this review, we summarize the current preclinical knowledge about the role of the sialic acid-Siglec interaction in immune suppression in cancer and discuss potential approaches to block this inhibitory pathway to enhance anti-cancer immunity.
近年来,包括免疫检查点抑制在内的免疫疗法改变了癌症疗法,为晚期患者提供了新的甚至可能治愈的选择。然而,只有少数患者能获得长期缓解,而且对免疫检查点抑制剂的耐药性也很常见。最近,人们提出了一种新的免疫检查点--sialic acid-Siglec 轴,它可以克服目前免疫疗法的抗药性。在这篇综述中,我们总结了目前临床前关于sialic acid-Siglec相互作用在癌症免疫抑制中作用的知识,并讨论了阻断这一抑制途径以增强抗癌免疫力的潜在方法。
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引用次数: 0
Shaping hematopoietic cell ecosystems through galectin-glycan interactions 通过加连蛋白-聚糖相互作用塑造造血细胞生态系统
IF 7.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.smim.2024.101889
Mirta Schattner , Bethan Psaila , Gabriel A. Rabinovich
Hematopoiesis- the formation of blood cell components- continually replenishes the blood system during embryonic development and postnatal lifespans. This coordinated process requires the synchronized action of a broad range of cell surface associated proteins and soluble mediators, including growth factors, cytokines and lectins. Collectively, these mediators control cellular communication, signalling, commitment, proliferation, survival and differentiation. Here we discuss the role of galectins – an evolutionarily conserved family of glycan-binding proteins – in the establishment and dynamic remodelling of hematopoietic niches. We focus on the contribution of galectins to B and T lymphocyte development and selection, as well as studies highlighting the role of these proteins in myelopoiesis, with particular emphasis on erythropoiesis and megakaryopoiesis. Finally, we also highlight recent findings suggesting the role of galectin-1, a prototype member of this protein family, as a key pathogenic factor and therapeutic target in myelofibrosis. Through extracellular or intracellular mechanisms, galectins can influence the fate and function of distinct hematopoietic progenitors and fine-tune the final repertoire of blood cells, with critical implications in a wide range of physiologically vital processes including innate and adaptive immunity, immune tolerance programs, tissue repair, regeneration, angiogenesis, inflammation, coagulation and oxygen delivery. Additionally, positive or negative regulation of galectin-driven circuits may contribute to a broad range of blood cell disorders.
造血--血细胞成分的形成--在胚胎发育和出生后的生命周期中不断补充血液系统。这一协调过程需要多种细胞表面相关蛋白和可溶性介质(包括生长因子、细胞因子和凝集素)的同步作用。这些介质共同控制着细胞通信、信号、承诺、增殖、存活和分化。在这里,我们将讨论半整联蛋白(进化保守的糖结合蛋白家族)在造血龛的建立和动态重塑中的作用。我们重点讨论了半整联蛋白对 B 淋巴细胞和 T 淋巴细胞发育和选择的贡献,以及强调这些蛋白在骨髓造血中作用的研究,尤其侧重于红细胞生成和巨核细胞生成。最后,我们还重点介绍了最近的研究结果,这些结果表明,该蛋白家族的原型成员 galectin-1 是骨髓纤维化的关键致病因素和治疗靶点。通过细胞外或细胞内机制,galectins 可影响不同造血祖细胞的命运和功能,并对血细胞的最终种类进行微调,从而对包括先天性和适应性免疫、免疫耐受程序、组织修复、再生、血管生成、炎症、凝血和氧输送在内的一系列重要生理过程产生重要影响。此外,galectin 驱动回路的正向或负向调节可能导致多种血细胞疾病。
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引用次数: 0
The role of sialoglycans in modulating dendritic cell function and tumour immunity 硅藻糖在调节树突状细胞功能和肿瘤免疫中的作用
IF 7.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-07-01 DOI: 10.1016/j.smim.2024.101900
Zélia Silva , Cátia O. Soares , Mariana Barbosa , Angelina S. Palma , Filipa Marcelo , Paula A. Videira
Dendritic cells (DCs) are crucial for initiating immune responses against tumours by presenting antigens to T cells. Glycosylation, particularly sialylation, plays a significant role in regulating cell functions, by modulating protein folding and signalling. This review aimed to provide a comprehensive overview of how sialic acids influence key aspects of DC biology, including maturation, migration, antigen presentation, and T cell interactions. Sialic acids influence DC endocytosis, affecting their ability to uptake and present antigens, while guiding their migration to lymph nodes and inflamed tissues. Removing sialic acids enhances DC-mediated antigen presentation to T cells, potentially boosting immune responses. Additionally, sialylated glycans on DCs modulate immune checkpoints, which can impact tumour immunity. Hypersialylation of tumour mucins further promotes immune evasion by interacting with DCs. Understanding the interplay between sialylation and DC functions offers promising avenues for enhancing cancer immunotherapy.
树突状细胞(DC)通过向 T 细胞展示抗原,对启动针对肿瘤的免疫反应至关重要。糖基化,尤其是ialylation,通过调节蛋白质折叠和信号传导,在调节细胞功能方面发挥着重要作用。本综述旨在全面概述硅烷酸如何影响直流电生物学的关键方面,包括成熟、迁移、抗原呈递和 T 细胞相互作用。硅酸影响直流细胞的内吞作用,影响其摄取和呈现抗原的能力,同时引导其向淋巴结和炎症组织迁移。去除ialic酸可增强DC介导的向T细胞呈递抗原的能力,从而增强免疫反应。此外,DC 上的糖基化聚糖还能调节免疫检查点,从而影响肿瘤免疫。肿瘤粘蛋白的高ialylation通过与DC相互作用,进一步促进免疫逃避。了解糖基化与直流电功能之间的相互作用为加强癌症免疫疗法提供了有希望的途径。
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引用次数: 0
The role of glycans in health and disease: Regulators of the interaction between gut microbiota and host immune system 聚糖在健康和疾病中的作用:肠道微生物群与宿主免疫系统相互作用的调节器。
IF 7.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-05-01 DOI: 10.1016/j.smim.2024.101891
Lucy I. Crouch , Cláudia S. Rodrigues , Cassie R. Bakshani , Leticia Tavares-Gomes , Joana Gaifem , Salomé S. Pinho
The human gut microbiota is home to a diverse collection of microorganisms that has co-evolved with the host immune system in which host-microbiota interactions are essential to preserve health and homeostasis. Evidence suggests that the perturbation of this symbiotic host-microbiome relationship contributes to the onset of major diseases such as chronic inflammatory diseases including Inflammatory Bowel Disease. The host glycocalyx (repertoire of glycans/sugar-chains at the surface of gut mucosa) constitutes a major biological and physical interface between the intestinal mucosa and microorganisms, as well as with the host immune system. Glycans are an essential niche for microbiota colonization and thus an important modulator of host-microorganism interactions both in homeostasis and in disease. In this review, we discuss the role of gut mucosa glycome as an instrumental pathway that regulates host-microbiome interactions in homeostasis but also in health to inflammation transition. We also discuss the power of mucosa glycosylation remodelling as an attractive preventive and therapeutic strategy to preserve gut homeostasis.
人类肠道微生物群是多种微生物的家园,它们与宿主免疫系统共同进化,宿主与微生物群之间的相互作用对维护健康和平衡至关重要。有证据表明,宿主与微生物群之间的这种共生关系受到干扰,会导致慢性炎症性疾病(包括炎症性肠病)等重大疾病的发生。宿主糖萼(肠道粘膜表面的聚糖/糖链)是肠道粘膜与微生物以及宿主免疫系统之间的主要生物和物理界面。聚糖是微生物群定植的一个重要生态位,因此是宿主与微生物在体内平衡和疾病中相互作用的一个重要调节器。在这篇综述中,我们将讨论肠道粘膜糖蛋白作为调节宿主-微生物群相互作用的重要途径在平衡和健康向炎症转变过程中的作用。我们还讨论了粘膜糖基化重塑作为一种有吸引力的预防和治疗策略在保护肠道稳态方面的作用。
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引用次数: 0
The origins, manifestations, and potential treatments of allergic disorders 过敏性疾病的起源、表现和潜在治疗方法
IF 7.8 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-05-01 DOI: 10.1016/j.smim.2024.101886
Donata Vercelli , Stephen J. Galli
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引用次数: 0
Durability of immune responses to SARS-CoV-2 infection and vaccination 感染 SARS-CoV-2 和接种疫苗后免疫反应的持久性
IF 7.8 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-05-01 DOI: 10.1016/j.smim.2024.101884
Mehul S. Suthar

Infection with SARS-CoV-2 in humans has caused a pandemic of unprecedented dimensions. SARS-CoV-2 is primarily transmitted through respiratory droplets and targets ciliated epithelial cells in the nasal cavity, trachea, and lungs by utilizing the cellular receptor angiotensin-converting enzyme 2 (ACE2). The innate immune response, including type I and III interferons, inflammatory cytokines (IL-6, TNF-α, IL-1β), innate immune cells (monocytes, DCs, neutrophils, natural killer cells), antibodies (IgG, sIgA, neutralizing antibodies), and adaptive immune cells (B cells, CD8+ and CD4+ T cells) play pivotal roles in mitigating COVID-19 disease. Broad and durable B-cell– and T-cell immunity elicited by infection and vaccination is essential for protection against severe disease, hospitalization and death. However, the emergence of SARS-CoV-2 variants that evade neutralizing antibodies continue to jeopardize vaccine efficacy. In this review, we highlight our understanding the infection- and vaccine-mediated humoral, B and T cell responses, the durability of the immune responses, and how variants continue to threaten the efficacy of SARS-CoV-2 vaccines.

人类感染 SARS-CoV-2 已造成前所未有的大流行。SARS-CoV-2 主要通过呼吸道飞沫传播,并利用细胞受体血管紧张素转换酶 2(ACE2)作用于鼻腔、气管和肺部的纤毛上皮细胞。先天性免疫反应,包括 I 型和 III 型干扰素、炎症细胞因子(IL-6、TNF-α、IL-1β)、先天性免疫细胞(单核细胞、DC、中性粒细胞、自然杀伤细胞)、抗体(IgG、sIgA、中和抗体)和适应性免疫细胞(B 细胞、CD8+ 和 CD4+ T 细胞)在减轻 COVID-19 疾病中发挥着关键作用。通过感染和接种疫苗产生的广泛而持久的 B 细胞和 T 细胞免疫对于防止严重疾病、住院和死亡至关重要。然而,逃避中和抗体的 SARS-CoV-2 变体的出现继续危及疫苗的效力。在这篇综述中,我们将重点介绍我们对感染和疫苗介导的体液、B 细胞和 T 细胞反应、免疫反应的持久性以及变种如何继续威胁 SARS-CoV-2 疫苗的有效性的理解。
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引用次数: 0
期刊
Seminars in Immunology
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