Yu Yunhong, Jiang Peng, Sun Pan, Su Na, Lin Fangzhao
Institute of Blood Transfusion, Chinese Academy of Medical Science and Peking Union Medical College, Chengdu, Sichuan 610052, P.R. China.
Exp Ther Med. 2021 Jul;22(1):693. doi: 10.3892/etm.2021.10125. Epub 2021 May 2.
Death receptor 3 (DR3) and its corresponding ligand, tumor necrosis factor-like ligand 1A (TL1A), belong to the tumor necrosis factor superfamily. Signaling via this receptor-ligand pair results in pro-inflammatory and anti-inflammatory effects. Effector lymphocytes can be activated to exert pro-inflammatory activity by triggering the DR3/TL1A pathway. By contrast, DR3/TL1A signaling also induces expansion of the suppressive function of regulatory T cells, which serve an important role in exerting anti-inflammatory functions and maintaining immune homeostasis. Preclinical evidence indicates that neutralizing and agonistic antibodies, as well as ligand-based approaches targeting the DR3/TL1A pathway, may be used to treat diseases, including inflammatory and immune-mediated diseases. Accumulating evidence has suggested that modulating the DR3/TL1A pathway is a promising therapeutic approach for patients with these diseases. This review discusses preclinical models to gauge the progress of therapeutic strategies for diseases involving the DR3/TL1A pathway to aid in drug development.
死亡受体3（DR3）及其相应配体肿瘤坏死因子样配体1A（TL1A）属于肿瘤坏死因子超家族。通过这一受体-配体对进行的信号传导会产生促炎和抗炎作用。效应淋巴细胞可通过触发DR3/TL1A途径被激活以发挥促炎活性。相比之下，DR3/TL1A信号传导还会诱导调节性T细胞抑制功能的扩展，调节性T细胞在发挥抗炎功能和维持免疫稳态方面发挥重要作用。临床前证据表明，中和抗体、激动性抗体以及针对DR3/TL1A途径的基于配体的方法可用于治疗包括炎症性和免疫介导性疾病在内的多种疾病。越来越多的证据表明，调节DR3/TL1A途径对这些疾病患者而言是一种有前景的治疗方法。本综述讨论了用于评估涉及DR3/TL1A途径疾病治疗策略进展的临床前模型，以助力药物研发。
