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. Herein, we aim 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. In conclusion, 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.

中文翻译：

---

靶向 TL1A 和 DR3：IBD 抗细胞因子治疗的新前沿


TNF 样细胞因子 1A （TL1A） 及其功能受体死亡域受体 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具有公认的作用;诱饵受体 DcR3 的额外存在表明细胞因子系统受到严格调节。TL1A：DR3 信号转导在炎症性肠病 （IBD） 发病机制中的重要性得到了几条趋同证据的支持。在此，我们旨在全面了解目前在 IBD 背景下关于 TL1A/DR3 系统的已知情况。TL1A 和 DR3 由细胞亚群表达，在肠道炎症的启动和维持中起重要作用，是效应免疫反应的有效通用共刺激剂，表明它们参与 IBD 的发病机制。最近的证据还支持 TL1A：DR3 通过调节 Tregs 和先天淋巴细胞发挥均质作用。TL1A 和 DR3 也由基质细胞表达，并可能导致炎症诱导或不依赖炎症的肠道纤维化。最后，发现具有功能后果的遗传多态性可能允许患者分层，包括对 TL1A 靶向治疗药物的不同反应。总之，TL1A：DR3 信号传导在肠道炎症的免疫途径中起着核心和多方面的作用，例如在 IBD 中观察到的免疫途径。这些证据为开发针对 IBD 中该配体-受体对的药物方法提供了基础。