靶向 TL1A 和 DR3:IBD 抗细胞因子疗法的新领域

IF 23 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Gut Pub Date : 2024-09-11 DOI:10.1136/gutjnl-2024-332504
Giorgos Bamias, Paola Menghini, Theresa T Pizarro, Fabio Cominelli
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引用次数: 0

摘要

TNF 样细胞因子 1A(TL1A)及其功能性受体死亡域受体 3(DR3)分别是 TNF 和 TNFR 超家族的成员,在调节先天性和适应性免疫反应中发挥着公认的作用;诱饵受体 DcR3 的额外存在表明细胞因子系统受到严格调控。TL1A和DR3由细胞亚群表达,在肠道炎症的启动和维持中发挥重要作用,是效应免疫反应的强效通用成本刺激因子,表明它们参与了IBD的发病机制。最近的证据还支持 TL1A:DR3 通过调节 Tregs 和先天性淋巴细胞发挥平衡作用。TL1A 和 DR3 也在基质细胞中表达,可能有助于炎症诱导型或炎症非依赖型肠纤维形成。最后,发现具有功能性后果的基因多态性可对患者进行分层,包括对 TL1A 靶向疗法的不同反应。TL1A:DR3 信号在导致肠道炎症(如 IBD 中观察到的炎症)的免疫学通路中发挥着多方面的核心作用。这些证据为开发针对 IBD 中这对配体-受体的药物方法奠定了基础。
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Targeting TL1A and DR3: the new frontier of anti-cytokine therapy in IBD
TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain receptor 3 (DR3), are members of the TNF and TNFR superfamilies, respectively, with recognised roles in regulating innate and adaptive immune responses; additional existence of a decoy receptor, DcR3, indicates a tightly regulated cytokine system. The significance of TL1A:DR3 signalling in the pathogenesis of inflammatory bowel disease (IBD) is supported by several converging lines of evidence.To provide a comprehensive understanding of what is currently known regarding the TL1A/DR3 system in the context of IBD.TL1A and DR3 are expressed by cellular subsets with important roles for the initiation and maintenance of intestinal inflammation, serving as potent universal costimulators of effector immune responses, indicating their participation in the pathogenesis of IBD. Recent evidence also supports a homoeostatic role for TL1A:DR3 via regulation of Tregs and innate lymphoid cells. TL1A and DR3 are also expressed by stromal cells and may contribute to inflammation-induced or inflammation-independent intestinal fibrogenesis. Finally, discovery of genetic polymorphisms with functional consequences may allow for patient stratification, including differential responses to TL1A-targeted therapeutics.TL1A:DR3 signalling plays a central and multifaceted role in the immunological pathways that underlie intestinal inflammation, such as that observed in IBD. Such evidence provides the foundation for developing pharmaceutical approaches targeting this ligand-receptor pair in IBD.
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来源期刊
Gut
Gut 医学-胃肠肝病学
CiteScore
45.70
自引率
2.40%
发文量
284
审稿时长
1.5 months
期刊介绍: Gut is a renowned international journal specializing in gastroenterology and hepatology, known for its high-quality clinical research covering the alimentary tract, liver, biliary tree, and pancreas. It offers authoritative and current coverage across all aspects of gastroenterology and hepatology, featuring articles on emerging disease mechanisms and innovative diagnostic and therapeutic approaches authored by leading experts. As the flagship journal of BMJ's gastroenterology portfolio, Gut is accompanied by two companion journals: Frontline Gastroenterology, focusing on education and practice-oriented papers, and BMJ Open Gastroenterology for open access original research.
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