Pub Date : 2024-12-24DOI: 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.
{"title":"Decoding the multifaceted roles of galectins in self-defense","authors":"Sachiko Sato , Jun Iwaki , Jun Hirabayashi","doi":"10.1016/j.smim.2024.101926","DOIUrl":"10.1016/j.smim.2024.101926","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101926"},"PeriodicalIF":7.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-19DOI: 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.
{"title":"Roles for Siglec-glycan interactions in regulating immune cells","authors":"Sung-Yao Lin , Edward N. Schmidt , Kei Takahashi-Yamashiro , Matthew S. Macauley","doi":"10.1016/j.smim.2024.101925","DOIUrl":"10.1016/j.smim.2024.101925","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101925"},"PeriodicalIF":7.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-18DOI: 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
{"title":"The complement system in clinical oncology: Applications, limitations and challenges","authors":"Daniel Ajona , Mark S. Cragg , Ruben Pio","doi":"10.1016/j.smim.2024.101921","DOIUrl":"10.1016/j.smim.2024.101921","url":null,"abstract":"<div><div>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</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101921"},"PeriodicalIF":7.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 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.
{"title":"Complement regulation in tumor immune evasion","authors":"Guijun Liu , Xuxiao He , Gaoxiang Zhao , Zhimin Lu","doi":"10.1016/j.smim.2024.101912","DOIUrl":"10.1016/j.smim.2024.101912","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"76 ","pages":"Article 101912"},"PeriodicalIF":7.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 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.
{"title":"The tissue glycome as regulator of immune activation and tolerance mediated by C-type lectins and Siglecs","authors":"Eleonora Nardini , Ernesto Rodriguez , Yvette van Kooyk","doi":"10.1016/j.smim.2024.101913","DOIUrl":"10.1016/j.smim.2024.101913","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"76 ","pages":"Article 101913"},"PeriodicalIF":7.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 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.
{"title":"Galectins and Host–Pathogen Interactions: The roles in viral infections","authors":"Sheng-Fang Wang , Hung-Lin Chen , Fu-Tong Liu","doi":"10.1016/j.smim.2024.101911","DOIUrl":"10.1016/j.smim.2024.101911","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"76 ","pages":"Article 101911"},"PeriodicalIF":7.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 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.
{"title":"ABO blood groups and galectins: Implications in transfusion medicine and innate immunity","authors":"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","doi":"10.1016/j.smim.2024.101892","DOIUrl":"10.1016/j.smim.2024.101892","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"74 ","pages":"Article 101892"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 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.
{"title":"NGS data analysis for molecular diagnosis of Inborn Errors of Immunity","authors":"XT Yang, WL Yang, YL Lau","doi":"10.1016/j.smim.2024.101901","DOIUrl":"10.1016/j.smim.2024.101901","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"74 ","pages":"Article 101901"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 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.
{"title":"Sialic acid and Siglec receptors in tumor immunity and immunotherapy","authors":"Natalia Rodrigues Mantuano , Heinz Läubli","doi":"10.1016/j.smim.2024.101893","DOIUrl":"10.1016/j.smim.2024.101893","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"74 ","pages":"Article 101893"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 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。
{"title":"Shaping hematopoietic cell ecosystems through galectin-glycan interactions","authors":"Mirta Schattner , Bethan Psaila , Gabriel A. Rabinovich","doi":"10.1016/j.smim.2024.101889","DOIUrl":"10.1016/j.smim.2024.101889","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"74 ","pages":"Article 101889"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}