Pub Date : 2024-06-01DOI: 10.1016/j.cytogfr.2024.03.003
Lian Zeng , Pengchao Hu , Yu Zhang , Mingyue Li , Yilin Zhao , Shiyong Li , Ailin Luo
Macrophage migration inhibitory factor (MIF) is a cytokine in the immune system, participated in both innate and adaptive immune responses. Except from immune cells, MIF is also secreted by a variety of non-immune cells, including hematopoietic cells, endothelial cells (ECs), and neurons. MIF plays a crucial role in various diseases, such as sepsis, rheumatoid arthritis, acute kidney injury, and neurodegenerative diseases. The role of MIF in the neuropathogenesis of cognitive impairment disorders is emphasized, as it recruits multiple inflammatory mediators, leading to activating microglia or astrocyte-derived neuroinflammation. Furthermore, it contributes to the cell death of neurons and ECs with the binding of apoptosis-inducing factor (AIF) through parthanatos-associated apoptosis-inducing factor nuclease (PAAN) / MIF pathway. This review comprehensively delves into the relationship between MIF and the neuropathogenesis of cognitive impairment disorders, providing a series of emerging MIF-targeted pharmaceuticals as potential treatments for cognitive impairment disorders.
{"title":"Macrophage migration inhibitor factor (MIF): Potential role in cognitive impairment disorders","authors":"Lian Zeng , Pengchao Hu , Yu Zhang , Mingyue Li , Yilin Zhao , Shiyong Li , Ailin Luo","doi":"10.1016/j.cytogfr.2024.03.003","DOIUrl":"10.1016/j.cytogfr.2024.03.003","url":null,"abstract":"<div><p>Macrophage migration inhibitory factor (MIF) is a cytokine in the immune system, participated in both innate and adaptive immune responses. Except from immune cells, MIF is also secreted by a variety of non-immune cells, including hematopoietic cells, endothelial cells (ECs), and neurons. MIF plays a crucial role in various diseases, such as sepsis, rheumatoid arthritis, acute kidney injury, and neurodegenerative diseases. The role of MIF in the neuropathogenesis of cognitive impairment disorders is emphasized, as it recruits multiple inflammatory mediators, leading to activating microglia or astrocyte-derived neuroinflammation. Furthermore, it contributes to the cell death of neurons and ECs with the binding of apoptosis-inducing factor (AIF) through parthanatos-associated apoptosis-inducing factor nuclease (PAAN) / MIF pathway. This review comprehensively delves into the relationship between MIF and the neuropathogenesis of cognitive impairment disorders, providing a series of emerging MIF-targeted pharmaceuticals as potential treatments for cognitive impairment disorders.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271342","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 : 2024-06-01DOI: 10.1016/j.cytogfr.2024.03.004
Simran Takkar , Gunjan Sharma , Jyoti B. Kaushal , K.M. Abdullah , Surinder K. Batra , Jawed A. Siddiqui
G protein-coupled receptors (GPCRs) are well-studied and the most traceable cell surface receptors for drug discovery. One of the intriguing members of this family is G protein-coupled receptors 35 (GPR35), which belongs to the class A rhodopsin-like family of GPCRs identified over two decades ago. GPR35 presents interesting features such as ubiquitous expression and distinct isoforms. Moreover, functional and genome-wide association studies on its widespread expression have linked GPR35 with pathophysiological disease progression. Various pieces of evidence have been accumulated regarding the independent or endogenous ligand-dependent role of GPR35 in cancer progression and metastasis. In the current scenario, the relationship of this versatile receptor and its putative endogenous ligands for the activation of oncogenic signal transduction pathways at the cellular level is an active area of research. These intriguing features offered by GPR35 make it an oncological target, justifying its uniqueness at the physiological and pathophysiological levels concerning other GPCRs. For pharmacologically targeting receptor-induced signaling, few potential competitive antagonists have been discovered that offer high selectivity at a human level. In addition to its fascinating features, targeting GPR35 at rodent and human orthologue levels is distinct, thus contributing to the sub-species selectivity. Strategies to modulate these issues will help us understand and truly target GPR35 at the therapeutic level. In this article, we have provided prospects on each topic mentioned above and suggestions to overcome the challenges. This review discusses the molecular mechanism and signal transduction pathways activated by endogenous ligands or spontaneous auto-activation of GPR35 that contributes towards disease progression. Furthermore, we have highlighted the GPR35 structure, ubiquitous expression, its role in immunomodulation, and at the pathophysiological level, especially in cancer, indicating its status as a versatile receptor. Subsequently, we discussed the various proposed ligands and their mechanism of interaction with GPR35. Additionally, we have summarized the GPR35 antagonist that provides insights into the opportunities for therapeutically targeting this receptor.
G 蛋白偶联受体(GPCR)是研究得最透彻的细胞表面受体,也是药物发现中最容易追踪的细胞表面受体。二十多年前发现的 G 蛋白偶联受体 35(GPR35)属于 GPCR 的 A 类视黄醛样家族,是这一家族中引人入胜的成员之一。GPR35 具有无处不在的表达和不同的同工型等有趣特征。此外,对其广泛表达的功能性和全基因组关联研究表明,GPR35 与病理生理疾病的进展有关。关于 GPR35 在癌症进展和转移中的独立或内源性配体依赖性作用,已经积累了各种证据。在目前的情况下,这种多用途受体及其假定的内源性配体在细胞水平激活致癌信号转导通路的关系是一个活跃的研究领域。GPR35 所具有的这些引人入胜的特点使其成为肿瘤靶点,并证明了它在生理和病理生理学水平上相对于其他 GPCR 的独特性。在以受体诱导信号为药物靶点方面,已发现的潜在竞争性拮抗剂中,只有少数能在人体水平上提供高选择性。除了其引人入胜的特点外,靶向啮齿动物和人类同源物水平的 GPR35 也各不相同,因此造成了亚种选择性。调节这些问题的策略将有助于我们了解并真正在治疗层面上靶向 GPR35。在本文中,我们对上述每个主题进行了展望,并提出了克服挑战的建议。本综述讨论了由内源性配体激活或 GPR35 自发自动激活导致疾病进展的分子机制和信号转导途径。此外,我们还强调了 GPR35 的结构、泛在表达、在免疫调节中的作用以及在病理生理学水平上的作用,尤其是在癌症中的作用,这表明它是一种多功能受体。随后,我们讨论了各种拟议配体及其与 GPR35 的相互作用机制。此外,我们还总结了 GPR35 拮抗剂,为针对该受体的治疗提供了机会。
{"title":"From orphan to oncogene: The role of GPR35 in cancer and immune modulation","authors":"Simran Takkar , Gunjan Sharma , Jyoti B. Kaushal , K.M. Abdullah , Surinder K. Batra , Jawed A. Siddiqui","doi":"10.1016/j.cytogfr.2024.03.004","DOIUrl":"10.1016/j.cytogfr.2024.03.004","url":null,"abstract":"<div><p>G protein-coupled receptors (GPCRs) are well-studied and the most traceable cell surface receptors for drug discovery. One of the intriguing members of this family is G protein-coupled receptors 35 (GPR35), which belongs to the class A rhodopsin-like family of GPCRs identified over two decades ago. GPR35 presents interesting features such as ubiquitous expression and distinct isoforms. Moreover, functional and genome-wide association studies on its widespread expression have linked GPR35 with pathophysiological disease progression. Various pieces of evidence have been accumulated regarding the independent or endogenous ligand-dependent role of GPR35 in cancer progression and metastasis. In the current scenario, the relationship of this versatile receptor and its putative endogenous ligands for the activation of oncogenic signal transduction pathways at the cellular level is an active area of research. These intriguing features offered by GPR35 make it an oncological target, justifying its uniqueness at the physiological and pathophysiological levels concerning other GPCRs. For pharmacologically targeting receptor-induced signaling, few potential competitive antagonists have been discovered that offer high selectivity at a human level. In addition to its fascinating features, targeting GPR35 at rodent and human orthologue levels is distinct, thus contributing to the sub-species selectivity. Strategies to modulate these issues will help us understand and truly target GPR35 at the therapeutic level. In this article, we have provided prospects on each topic mentioned above and suggestions to overcome the challenges. This review discusses the molecular mechanism and signal transduction pathways activated by endogenous ligands or spontaneous auto-activation of GPR35 that contributes towards disease progression. Furthermore, we have highlighted the GPR35 structure, ubiquitous expression, its role in immunomodulation, and at the pathophysiological level, especially in cancer, indicating its status as a versatile receptor. Subsequently, we discussed the various proposed ligands and their mechanism of interaction with GPR35. Additionally, we have summarized the GPR35 antagonist that provides insights into the opportunities for therapeutically targeting this receptor.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184000","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 : 2024-06-01DOI: 10.1016/j.cytogfr.2024.01.003
Rou Zheng , Yan Ren , Xinyue Liu , Canxia He , Hua Liu , Yixuan Wang , Jianing Li , Shuya Xia , Zhifang Liu , Yizhao Ma , Dianchen Wang , Suling Xu , Geng Wang , Na Li
Atopic dermatitis (AD) is an inflammatory skin disease characterized by intense pruritus. AD is harmful to both children and adults, but its pathogenic mechanism has yet to be fully elucidated. The development of mouse models for AD has greatly contributed to its study and treatment. Among these models, the exogenous drug-induced mouse model has shown promising results and significant advantages. Until now, a large amount of AD-related research has utilized exogenous drug-induced mouse models, leading to notable advancements in research. This indicates the crucial significance of applying such models in AD research. These models exhibit diverse characteristics and are highly complex. They involve the use of various strains of mice, diverse types of inducers, and different modeling effects. However, there is currently a lack of comprehensive comparative studies on exogenous drug-induced AD mouse models, which hinders researchers' ability to choose among these models. This paper provides a comprehensive review of the features and mechanisms associated with various exogenous drug-induced mouse models, including the important role of each cytokine in AD development. It aims to assist researchers in quickly understanding models and selecting the most suitable one for further investigation.
特应性皮炎(AD)是一种以剧烈瘙痒为特征的炎症性皮肤病。特应性皮炎对儿童和成人都有害,但其致病机制尚未完全阐明。小鼠皮炎模型的开发极大地促进了皮炎的研究和治疗。在这些模型中,外源性药物诱导小鼠模型显示出了良好的效果和显著的优势。迄今为止,大量与阿德相关的研究都采用了外源性药物诱导小鼠模型,从而取得了显著的研究进展。这表明将此类模型应用于注意力缺失症研究具有至关重要的意义。这些模型表现出多种多样的特点,而且非常复杂。它们涉及使用不同品系的小鼠、不同类型的诱导剂和不同的建模效果。然而,目前缺乏关于外源性药物诱导的 AD 小鼠模型的全面比较研究,这阻碍了研究人员在这些模型中进行选择。本文全面综述了各种外源性药物诱导的小鼠模型的特点和相关机制,包括每种细胞因子在AD发展过程中的重要作用。它旨在帮助研究人员快速了解模型,并选择最合适的模型进行进一步研究。
{"title":"Exogenous drug-induced mouse models of atopic dermatitis","authors":"Rou Zheng , Yan Ren , Xinyue Liu , Canxia He , Hua Liu , Yixuan Wang , Jianing Li , Shuya Xia , Zhifang Liu , Yizhao Ma , Dianchen Wang , Suling Xu , Geng Wang , Na Li","doi":"10.1016/j.cytogfr.2024.01.003","DOIUrl":"10.1016/j.cytogfr.2024.01.003","url":null,"abstract":"<div><p>Atopic dermatitis (AD) is an inflammatory skin disease characterized by intense pruritus. AD is harmful to both children and adults, but its pathogenic mechanism has yet to be fully elucidated. The development of mouse models for AD has greatly contributed to its study and treatment. Among these models, the exogenous drug-induced mouse model has shown promising results and significant advantages. Until now, a large amount of AD-related research has utilized exogenous drug-induced mouse models, leading to notable advancements in research. This indicates the crucial significance of applying such models in AD research. These models exhibit diverse characteristics and are highly complex. They involve the use of various strains of mice, diverse types of inducers, and different modeling effects. However, there is currently a lack of comprehensive comparative studies on exogenous drug-induced AD mouse models, which hinders researchers' ability to choose among these models. This paper provides a comprehensive review of the features and mechanisms associated with various exogenous drug-induced mouse models, including the important role of each cytokine in AD development. It aims to assist researchers in quickly understanding models and selecting the most suitable one for further investigation.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139463027","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 : 2024-06-01DOI: 10.1016/j.cytogfr.2024.03.005
Qixiang Song , Yuhang Fan , Huali Zhang , Nian Wang
Innate immunity is not only the first line of host defense against microbial infections but is also crucial for the host responses against a variety of noxious stimuli. Z-DNA binding protein 1 (ZBP1) is a cytosolic nucleic acid sensor that can induce inflammatory cell death in both immune and nonimmune cells upon sensing of incursive virus-derived Z-form nucleic acids and self-nucleic acids via its Zα domain. Mechanistically, aberrantly expressed or activated ZBP1 induced by pathogens or noxious stimuli enables recruitment of TANK binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3 to drive type I interferon (IFN-I) responses and activation of nuclear factor kappa B (NF-κB) signaling. Meanwhile, ZBP1 promotes the assembly of ZBP1- and absent in melanoma 2 (AIM2)-PANoptosome, which ultimately triggers PANoptosis through caspase 3-mediated apoptosis, mixed lineage kinase domain like pseudokinase (MLKL)-mediated necroptosis, and gasdermin D (GSDMD)-mediated pyroptosis. In response to damaged mitochondrial DNA, ZBP1 can interact with cyclic GMP-AMP synthase to augment IFN-I responses but inhibits toll like receptor 9-mediated inflammatory responses. This review summarizes the structure and expression pattern of ZBP1, discusses its roles in human diseases through immune-dependent (e.g., the production of IFN-I and pro-inflammatory cytokines) and -independent (e.g., the activation of cell death) functions, and highlights the attractive prospect of manipulating ZBP1 as a promising therapeutic target in diseases.
{"title":"Z-DNA binding protein 1 orchestrates innate immunity and inflammatory cell death","authors":"Qixiang Song , Yuhang Fan , Huali Zhang , Nian Wang","doi":"10.1016/j.cytogfr.2024.03.005","DOIUrl":"10.1016/j.cytogfr.2024.03.005","url":null,"abstract":"<div><p>Innate immunity is not only the first line of host defense against microbial infections but is also crucial for the host responses against a variety of noxious stimuli. Z-DNA binding protein 1 (ZBP1) is a cytosolic nucleic acid sensor that can induce inflammatory cell death in both immune and nonimmune cells upon sensing of incursive virus-derived Z-form nucleic acids and self-nucleic acids via its Zα domain. Mechanistically, aberrantly expressed or activated ZBP1 induced by pathogens or noxious stimuli enables recruitment of TANK binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3 to drive type I interferon (IFN-I) responses and activation of nuclear factor kappa B (NF-κB) signaling. Meanwhile, ZBP1 promotes the assembly of ZBP1- and absent in melanoma 2 (AIM2)-PANoptosome, which ultimately triggers PANoptosis through caspase 3-mediated apoptosis, mixed lineage kinase domain like pseudokinase (MLKL)-mediated necroptosis, and gasdermin D (GSDMD)-mediated pyroptosis. In response to damaged mitochondrial DNA, ZBP1 can interact with cyclic GMP-AMP synthase to augment IFN-I responses but inhibits toll like receptor 9-mediated inflammatory responses. This review summarizes the structure and expression pattern of ZBP1, discusses its roles in human diseases through immune-dependent (<em>e.g.</em>, the production of IFN-I and pro-inflammatory cytokines) and -independent (<em>e.g.</em>, the activation of cell death) functions, and highlights the attractive prospect of manipulating ZBP1 as a promising therapeutic target in diseases.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317987","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 : 2024-06-01DOI: 10.1016/j.cytogfr.2024.03.001
Lu Jiang , Zirui Wang , Ting Xu , Leiliang Zhang
Pyroptosis, a programmed cell death process, is vital for the immune response against microbial infections and internal danger signals. Recent studies have highlighted the importance of protein palmitoylation, a modification that involves attaching palmitate to cysteine residues, in regulating key proteins involved in pyroptosis. Palmitoylation of cGAS at residue C474 by ZDHHC18 affects its enzymatic activity and DNA binding ability. Similarly, ZDHHC9 promotes cGAS activity through palmitoylation at residues C404/405. NLRP3 palmitoylation at residue C844, mediated by ZDHHC12, impacts its stability and interactions with other proteins, crucial for activating the NLRP3 inflammasome and triggering inflammation. However, the role of ZDHHC5 in NLRP3 palmitoylation remains uncertain due to conflicting findings. Palmitoylation at C88/91 is essential for STING activation and induction of type I interferons. It modulates the formation of multimeric complexes and downstream signaling pathways. GSDMD palmitoylation at C191 is necessary for pore formation and membrane translocation, while GSDME palmitoylation at C407/408 is associated with drug-induced pyroptosis. Moreover, palmitoylation of NOD1 and NOD2 influences their membrane recruitment and immune signaling pathways in response to bacterial peptidoglycans, acting as upstream regulators of pyroptosis. This review summarizes the important roles for palmitoylation in regulating the function of key pyroptosis-related proteins, shedding light on the intricate mechanisms governing immune responses and inflammation.
{"title":"When pyro(ptosis) meets palm(itoylation)","authors":"Lu Jiang , Zirui Wang , Ting Xu , Leiliang Zhang","doi":"10.1016/j.cytogfr.2024.03.001","DOIUrl":"10.1016/j.cytogfr.2024.03.001","url":null,"abstract":"<div><p>Pyroptosis, a programmed cell death process, is vital for the immune response against microbial infections and internal danger signals. Recent studies have highlighted the importance of protein palmitoylation, a modification that involves attaching palmitate to cysteine residues, in regulating key proteins involved in pyroptosis. Palmitoylation of cGAS at residue C474 by ZDHHC18 affects its enzymatic activity and DNA binding ability. Similarly, ZDHHC9 promotes cGAS activity through palmitoylation at residues C404/405. NLRP3 palmitoylation at residue C844, mediated by ZDHHC12, impacts its stability and interactions with other proteins, crucial for activating the NLRP3 inflammasome and triggering inflammation. However, the role of ZDHHC5 in NLRP3 palmitoylation remains uncertain due to conflicting findings. Palmitoylation at C88/91 is essential for STING activation and induction of type I interferons. It modulates the formation of multimeric complexes and downstream signaling pathways. GSDMD palmitoylation at C191 is necessary for pore formation and membrane translocation, while GSDME palmitoylation at C407/408 is associated with drug-induced pyroptosis. Moreover, palmitoylation of NOD1 and NOD2 influences their membrane recruitment and immune signaling pathways in response to bacterial peptidoglycans, acting as upstream regulators of pyroptosis. This review summarizes the important roles for palmitoylation in regulating the function of key pyroptosis-related proteins, shedding light on the intricate mechanisms governing immune responses and inflammation.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054973","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 : 2024-06-01DOI: 10.1016/j.cytogfr.2024.04.001
Aleksandra Gędaj, Paulina Gregorczyk, Dominika Żukowska, Aleksandra Chorążewska, Krzysztof Ciura, Marta Kalka, Natalia Porębska, Łukasz Opaliński
Fibroblast growth factors (FGFs) and their receptors (FGFRs) constitute plasma-membrane localized signaling hubs that transmit signals from the extracellular environment to the cell interior, governing pivotal cellular processes like motility, metabolism, differentiation, division and death. FGF/FGFR signaling is critical for human body development and homeostasis; dysregulation of FGF/FGFR units is observed in numerous developmental diseases and in about 10% of human cancers. Glycosylation is a highly abundant posttranslational modification that is critical for physiological and pathological functions of the cell. Glycosylation is also very common within FGF/FGFR signaling hubs. Vast majority of FGFs (15 out of 22 members) are N-glycosylated and few FGFs are O-glycosylated. Glycosylation is even more abundant within FGFRs; all FGFRs are heavily N-glycosylated in numerous positions within their extracellular domains. A growing number of studies points on the multiple roles of glycosylation in fine-tuning FGF/FGFR signaling. Glycosylation modifies secretion of FGFs, determines their stability and affects interaction with FGFRs and co-receptors. Glycosylation of FGFRs determines their intracellular sorting, constitutes autoinhibitory mechanism within FGFRs and adjusts FGF and co-receptor recognition. Sugar chains attached to FGFs and FGFRs constitute also a form of code that is differentially decrypted by extracellular lectins, galectins, which transform FGF/FGFR signaling at multiple levels. This review focuses on the identified functions of glycosylation within FGFs and FGFRs and discusses their relevance for the cell physiology in health and disease.
{"title":"Glycosylation of FGF/FGFR: An underrated sweet code regulating cellular signaling programs","authors":"Aleksandra Gędaj, Paulina Gregorczyk, Dominika Żukowska, Aleksandra Chorążewska, Krzysztof Ciura, Marta Kalka, Natalia Porębska, Łukasz Opaliński","doi":"10.1016/j.cytogfr.2024.04.001","DOIUrl":"10.1016/j.cytogfr.2024.04.001","url":null,"abstract":"<div><p>Fibroblast growth factors (FGFs) and their receptors (FGFRs) constitute plasma-membrane localized signaling hubs that transmit signals from the extracellular environment to the cell interior, governing pivotal cellular processes like motility, metabolism, differentiation, division and death. FGF/FGFR signaling is critical for human body development and homeostasis; dysregulation of FGF/FGFR units is observed in numerous developmental diseases and in about 10% of human cancers. Glycosylation is a highly abundant posttranslational modification that is critical for physiological and pathological functions of the cell. Glycosylation is also very common within FGF/FGFR signaling hubs. Vast majority of FGFs (15 out of 22 members) are N-glycosylated and few FGFs are O-glycosylated. Glycosylation is even more abundant within FGFRs; all FGFRs are heavily N-glycosylated in numerous positions within their extracellular domains. A growing number of studies points on the multiple roles of glycosylation in fine-tuning FGF/FGFR signaling. Glycosylation modifies secretion of FGFs, determines their stability and affects interaction with FGFRs and co-receptors. Glycosylation of FGFRs determines their intracellular sorting, constitutes autoinhibitory mechanism within FGFRs and adjusts FGF and co-receptor recognition. Sugar chains attached to FGFs and FGFRs constitute also a form of code that is differentially decrypted by extracellular lectins, galectins, which transform FGF/FGFR signaling at multiple levels. This review focuses on the identified functions of glycosylation within FGFs and FGFRs and discusses their relevance for the cell physiology in health and disease.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359610124000340/pdfft?md5=e4b6fce3e729f559c586c05301ce1a09&pid=1-s2.0-S1359610124000340-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891806","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 : 2024-06-01DOI: 10.1016/j.cytogfr.2024.03.002
Urban Švajger , Urška Kamenšek
The tumor microenvironment is importantly shaped by various cytokines, where interleukins (ILs) and interferons (IFNs) shape the balance of immune activity within tumor niche and associated lymphoid organs. Their importance in activation and tuning of both innate and adaptive immune responses prompted their use in several clinical trials, albeit with limited therapeutic efficacy and risk of toxicity due to systemic administration. Increasing preclinical evidence suggests that local delivery of ILs and IFNs could significantly increase their effectiveness, while simultaneously attenuate the known side effects and issues related to their biological activity. A prominent way to achieve this is to use cell-based delivery vehicles. For this purpose, mesenchymal stromal stem cells (MSCs) are considered an almost ideal candidate. Namely, MSCs can be obtained in large quantities and from obtainable sources (e.g. umbilical cord or adipose tissue), their ex vivo expansion is relatively straightforward compared to other cell types and they possess very low immunogenicity making them suitable for allogeneic use. Importantly, MSCs have shown an intrinsic capacity to respond to tumor-directed chemotaxis. This review provides a focused and detailed discussion on MSC-based gene therapy using ILs and IFNs, engineering techniques and insights on potential future advancements.
各种细胞因子对肿瘤微环境起着重要作用,其中白细胞介素(ILs)和干扰素(IFNs)决定着肿瘤龛和相关淋巴器官内免疫活动的平衡。白细胞介素和干扰素在激活和调整先天性免疫反应和适应性免疫反应方面具有重要作用,这促使它们被用于多项临床试验,尽管疗效有限,而且由于全身给药还存在毒性风险。越来越多的临床前证据表明,ILs 和 IFNs 的局部给药可以显著提高它们的疗效,同时减轻已知的副作用和与它们的生物活性有关的问题。实现这一目标的一个重要方法是使用基于细胞的递送载体。为此,间充质基质干细胞(MSCs)被认为是几乎理想的候选者。也就是说,间充质干细胞可以从可获得的来源(如脐带或脂肪组织)中大量获得,与其他细胞类型相比,间充质干细胞的体外扩增相对简单,而且间充质干细胞的免疫原性很低,适合异体使用。重要的是,间充质干细胞具有对肿瘤引导的趋化做出反应的内在能力。本综述重点详细讨论了使用 ILs 和 IFNs 的间充质干细胞基因疗法、工程技术以及对未来潜在进展的见解。
{"title":"Interleukins and interferons in mesenchymal stromal stem cell-based gene therapy of cancer","authors":"Urban Švajger , Urška Kamenšek","doi":"10.1016/j.cytogfr.2024.03.002","DOIUrl":"10.1016/j.cytogfr.2024.03.002","url":null,"abstract":"<div><p>The tumor microenvironment is importantly shaped by various cytokines, where interleukins (ILs) and interferons (IFNs) shape the balance of immune activity within tumor niche and associated lymphoid organs. Their importance in activation and tuning of both innate and adaptive immune responses prompted their use in several clinical trials, albeit with limited therapeutic efficacy and risk of toxicity due to systemic administration. Increasing preclinical evidence suggests that local delivery of ILs and IFNs could significantly increase their effectiveness, while simultaneously attenuate the known side effects and issues related to their biological activity. A prominent way to achieve this is to use cell-based delivery vehicles. For this purpose, mesenchymal stromal stem cells (MSCs) are considered an almost ideal candidate. Namely, MSCs can be obtained in large quantities and from obtainable sources (e.g. umbilical cord or adipose tissue), their <em>ex vivo</em> expansion is relatively straightforward compared to other cell types and they possess very low immunogenicity making them suitable for allogeneic use. Importantly, MSCs have shown an intrinsic capacity to respond to tumor-directed chemotaxis. This review provides a focused and detailed discussion on MSC-based gene therapy using ILs and IFNs, engineering techniques and insights on potential future advancements.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174106","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 : 2024-06-01DOI: 10.1016/j.cytogfr.2024.05.001
Kexin Jiang , Yanjiani Xu , Yan Wang , Nanhao Yin , Fangyang Huang , Mao Chen
Interleukin-17 (IL-17), a pivotal cytokine in immune regulation, has attracted significant attention in recent years due to its roles in various physiological and pathological processes. This review explores IL-17 in immunological context, emphasizing its structure, production, and signaling pathways. Specifically, we explore its involvement in inflammatory diseases and autoimmune diseases, with a notable focus on its emerging implications in cardiovascular system. Through an array of research insights, IL-17 displays multifaceted functions yet awaiting comprehensive discovery. Highlighting therapeutic avenues, we scrutinize the efficacy and clinical application of four marketed IL-17 mAbs along other targeted therapies, emphasizing their potential in immune-mediated disease management. Additionally, we discussed the novel IL-17D-CD93 axis, elucidating recent breakthroughs in their biological function and clinical implications, inviting prospects for transformative advancements in immunology and beyond.
{"title":"Unveiling the role of IL-17: Therapeutic insights and cardiovascular implications","authors":"Kexin Jiang , Yanjiani Xu , Yan Wang , Nanhao Yin , Fangyang Huang , Mao Chen","doi":"10.1016/j.cytogfr.2024.05.001","DOIUrl":"10.1016/j.cytogfr.2024.05.001","url":null,"abstract":"<div><p>Interleukin-17 (IL-17), a pivotal cytokine in immune regulation, has attracted significant attention in recent years due to its roles in various physiological and pathological processes. This review explores IL-17 in immunological context, emphasizing its structure, production, and signaling pathways. Specifically, we explore its involvement in inflammatory diseases and autoimmune diseases, with a notable focus on its emerging implications in cardiovascular system. Through an array of research insights, IL-17 displays multifaceted functions yet awaiting comprehensive discovery. Highlighting therapeutic avenues, we scrutinize the efficacy and clinical application of four marketed IL-17 mAbs along other targeted therapies, emphasizing their potential in immune-mediated disease management. Additionally, we discussed the novel IL-17D-CD93 axis, elucidating recent breakthroughs in their biological function and clinical implications, inviting prospects for transformative advancements in immunology and beyond.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912135","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 : 2024-02-28DOI: 10.1016/j.cytogfr.2024.02.003
Suling Xu , Qingqing Wang , Wenxue Ma
Navigating the intricate landscape of the tumor microenvironment (TME) unveils a pivotal arena for cancer therapeutics, where cytokines and soluble mediators emerge as double-edged swords in the fight against cancer. This review ventures beyond traditional perspectives, illuminating the nuanced interplay of these elements as both allies and adversaries in cancer dynamics. It critically evaluates the evolving paradigms of TME reprogramming, spotlighting innovative strategies that target the sophisticated network of cytokines and mediators. Special focus is placed on unveiling the therapeutic potential of novel cytokines and mediators, particularly their synergistic interactions with extracellular vesicles, which represent underexplored conduits for therapeutic targeting. Addressing a significant gap in current research, we explore the untapped potential of these biochemical players in orchestrating immune responses, tumor proliferation, and metastasis. The review advocates for a paradigm shift towards exploiting these dynamic interactions within the TME, aiming to transcend conventional treatments and pave the way for a new era of precision oncology. Through a critical synthesis of recent advancements, we highlight the imperative for innovative approaches that harness the full spectrum of cytokine and mediator activities, setting the stage for breakthrough therapies that offer heightened specificity, reduced toxicity, and improved patient outcomes.
{"title":"Cytokines and soluble mediators as architects of tumor microenvironment reprogramming in cancer therapy","authors":"Suling Xu , Qingqing Wang , Wenxue Ma","doi":"10.1016/j.cytogfr.2024.02.003","DOIUrl":"10.1016/j.cytogfr.2024.02.003","url":null,"abstract":"<div><p>Navigating the intricate landscape of the tumor microenvironment (TME) unveils a pivotal arena for cancer therapeutics, where cytokines and soluble mediators emerge as double-edged swords in the fight against cancer. This review ventures beyond traditional perspectives, illuminating the nuanced interplay of these elements as both allies and adversaries in cancer dynamics. It critically evaluates the evolving paradigms of TME reprogramming, spotlighting innovative strategies that target the sophisticated network of cytokines and mediators. Special focus is placed on unveiling the therapeutic potential of novel cytokines and mediators, particularly their synergistic interactions with extracellular vesicles, which represent underexplored conduits for therapeutic targeting. Addressing a significant gap in current research, we explore the untapped potential of these biochemical players in orchestrating immune responses, tumor proliferation, and metastasis. The review advocates for a paradigm shift towards exploiting these dynamic interactions within the TME, aiming to transcend conventional treatments and pave the way for a new era of precision oncology. Through a critical synthesis of recent advancements, we highlight the imperative for innovative approaches that harness the full spectrum of cytokine and mediator activities, setting the stage for breakthrough therapies that offer heightened specificity, reduced toxicity, and improved patient outcomes.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140016975","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}