Seminars in Immunology最新文献

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Decoding the multifaceted roles of galectins in self-defense 解读凝集素在自卫中的多重作用。

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2024-12-24 DOI: 10.1016/j.smim.2024.101926

Sachiko Sato , Jun Iwaki , Jun Hirabayashi

In this review, we aim to explore the multifaceted roles of galectins in host defense from a broader perspective, particularly regarding their functions when host integrity is compromised. Numerous comprehensive reviews on galectin functions in immunity have already been published. For researchers new to the field, this wealth of information may create an impression of galectins as proteins involved in a wide array of biological processes. Furthermore, due to the heterogeneity of galectin ligands, glycans, there is a risk of perceiving galectin-specific functions as ambiguous, potentially obscuring their core biological significance. To address this, we revisit foundational aspects, focusing on the significance of the recognition of galactose, a “late-comer” monosaccharide in evolutionary terms, provide an overview of galectin glycan binding specificity, with emphasis on the potential biological importance of each carbohydrate-recognition domain. We also discuss the biological implications of the galectin location paradox wherein these cytosolic lectins function in host defense despite their glycan ligands being synthesized in the secretory pathway. Additionally, we examine the role of galectins in liquid-liquid phase separation on membranes, which may facilitate their diverse functions in cellular responses. Through this approach, we aim to re-evaluate the complex and diverse biological roles of galectins in host defense.

在这篇综述中，我们旨在从更广泛的角度探讨聚集素在宿主防御中的多方面作用，特别是当宿主完整性受到损害时它们的功能。许多关于凝集素在免疫中的功能的综合综述已经发表。对于刚进入该领域的研究人员来说，这些丰富的信息可能会给他们留下这样的印象：凝集素是一种参与广泛生物过程的蛋白质。此外，由于半乳糖凝集素配体（甘聚糖）的异质性，存在将半乳糖凝集素特异性功能视为模糊的风险，潜在地模糊了其核心生物学意义。为了解决这个问题，我们回顾了基础方面，重点关注半乳糖识别的重要性，半乳糖是进化方面的“后来者”单糖，提供了半乳糖聚糖结合特异性的概述，强调了每个碳水化合物识别结构域的潜在生物学重要性。我们还讨论了凝集素位置悖论的生物学意义，其中这些细胞质凝集素在宿主防御中起作用，尽管它们的聚糖配体是在分泌途径中合成的。此外，我们研究了凝集素在膜上液液相分离中的作用，这可能有助于它们在细胞反应中的多种功能。通过这种方法，我们旨在重新评估凝集素在宿主防御中的复杂和多样的生物学作用。

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引用次数: 0

Roles for Siglec-glycan interactions in regulating immune cells sigle -glycan相互作用在调节免疫细胞中的作用。

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2024-12-19 DOI: 10.1016/j.smim.2024.101925

Sung-Yao Lin , Edward N. Schmidt , Kei Takahashi-Yamashiro , Matthew S. Macauley

Cell surface complex carbohydrates, known as glycans, are positioned to be the first point of contact between two cells. Indeed, interactions between glycans with glycan-binding can modulate cell-cell interactions. This concept is particularly relevant for immune cells, which use an array of glycan-binding proteins to help in the process of differentiating ‘self’ from ‘non-self’. This is exemplified by the sialic acid-binding immunoglobulin-type lectins (Siglecs), which recognize sialic acid. Given that sialic acid is relatively unique to vertebrates, immune cells leverage Siglecs to recognize sialic acid as a marker of ‘self’. Siglecs serve many biological roles, with most of these functions regulated through interactions with their sialoglycan ligands. In this review, we provide a comprehensive update on the ligands of Siglecs and how Siglec-sialoglycan interactions help regulate immune cells in the adaptive and innate immune system.

细胞表面复杂的碳水化合物，被称为聚糖，被定位为两个细胞之间的第一个接触点。实际上，聚糖与聚糖结合的相互作用可以调节细胞间的相互作用。这个概念与免疫细胞特别相关，免疫细胞使用一系列聚糖结合蛋白来帮助区分“自我”和“非自我”。唾液酸结合免疫球蛋白型凝集素（Siglecs）就是一个例子，它能识别唾液酸。鉴于唾液酸对脊椎动物来说是相对独特的，免疫细胞利用Siglecs来识别唾液酸作为“自我”的标记。Siglecs具有许多生物学作用，其中大部分功能通过与其唾液聚糖配体的相互作用来调节。在这篇综述中，我们提供了Siglecs配体的全面更新，以及Siglecs -唾液聚糖相互作用如何帮助调节适应性和先天免疫系统中的免疫细胞。

引用次数: 0

The complement system in clinical oncology: Applications, limitations and challenges 补体系统在临床肿瘤学中的应用、限制和挑战。

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2024-12-18 DOI: 10.1016/j.smim.2024.101921

Daniel Ajona , Mark S. Cragg , Ruben Pio

The complement system, a key component of innate immunity, is involved in seemingly contradictory aspects of tumor progression and cancer therapy. It can act as an immune effector against cancer and modulate the antitumor activity of certain therapeutic antibodies, but it can also contribute to a tumor-promoting microenvironment. Understanding this dual role should lead to the development of better therapeutic tools, strategies for cancer treatment and biomarkers for the clinical management of cancer patients. Here, we review recent advances in the understanding of the role of complement in cancer, focusing on how these findings are being translated into the clinic. We highlight the activity of therapeutic agents that modulate the complement system, as well as combination therapies that integrate complement modulation with existing therapies. We conclude that the role of complement activation in cancer is a rapidly evolving field with the potential to translate findings into new therapeutic strategies and clinically useful biomarkers

补体系统是先天免疫的关键组成部分，它参与了肿瘤进展和癌症治疗的看似矛盾的方面。它可以作为抗癌的免疫效应物，调节某些治疗性抗体的抗肿瘤活性，但它也可以促进肿瘤的微环境。了解这种双重作用将有助于开发更好的治疗工具、癌症治疗策略和癌症患者临床管理的生物标志物。在这里，我们回顾了补体在癌症中的作用的最新进展，重点是这些发现是如何转化为临床的。我们强调了调节补体系统的治疗药物的活性，以及将补体调节与现有疗法相结合的联合疗法。我们的结论是，补体活化在癌症中的作用是一个快速发展的领域，有可能将研究结果转化为新的治疗策略和临床有用的生物标志物。

引用次数: 0

Complement regulation in tumor immune evasion 肿瘤免疫逃避中的补体调节。

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2024-11-01 DOI: 10.1016/j.smim.2024.101912

Guijun Liu , Xuxiao He , Gaoxiang Zhao , Zhimin Lu

The complement system plays crucial roles in both innate and adaptive immune responses, facilitating the elimination of pathogens such as microorganisms and damaged cells, including cancer cells. It is tightly regulated and integrated with cell-mediated immunity. In the tumor microenvironment, the complement system performs both immune and nonimmune functions in tumor and immune cells through pathways that depend on or are independent of complement activation, thereby promoting immune evasion and tumor progression.

补体系统在先天性免疫反应和适应性免疫反应中都发挥着至关重要的作用，有助于消灭微生物等病原体和包括癌细胞在内的受损细胞。补体系统受到严格调控，并与细胞介导免疫相结合。在肿瘤微环境中，补体系统通过依赖或独立于补体激活的途径，在肿瘤和免疫细胞中发挥免疫和非免疫功能，从而促进免疫逃避和肿瘤进展。

引用次数: 0

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

Seminars in 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

Seminars in 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。

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

Seminars in 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

Seminars in 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。

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

Seminars in 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。

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

Seminars in 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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