aAcademic Department of Gastroenterology, Ethnikon and Kapodistriakon University of Athens, Laikon Hospital, Athens, Greece bDivision of Gastrointestinal and Liver Disease, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA.
Curr Opin Gastroenterol. 2013 Nov;29(6):597-602. doi: 10.1097/MOG.0b013e328365d3a2.
Tumor necrosis factor (TNF)-like cytokine 1A (TL1A) associates with the death receptor 3 (DR3) on activated lymphocytes and induces proinflammatory signals. The decoy receptor 3 (DcR3) competes for TL1A binding and inhibits functional signaling. This review focuses on the role of the TL1A/DR3/DcR3 cytokine system in inflammatory bowel diseases (IBDs).
TL1A may induce IFN-γ-mediated and IL-17-mediated proinflammatory pathways in IBDs by acting on DR3-expressing, CD4(+)CD161(+) lymphocytes, which are substantially enriched at the inflamed intestinal mucosa. In addition, TL1A/DR3 signaling results in expansion of the Treg pool with concomitant and transient inhibition of their suppressive function. Constitutive expression of TL1A in transgenic mice was associated with small intestinal inflammation, which was accompanied by colonic fibrosis both spontaneously and under colitogenic conditions. Recent human studies demonstrated that soluble TL1A and DcR3 are present in the systemic circulation in patients with active IBD and decline after successful anti-inflammatory treatment.
TL1A/DR3 interactions may participate in the pathogenesis of chronic intestinal inflammation and offer novel therapeutic targets for patients with ulcerative colitis and Crohn's disease.
肿瘤坏死因子（TNF）样细胞因子 1A（TL1A）与活化淋巴细胞上的死亡受体 3（DR3）结合，并诱导促炎信号。诱饵受体 3（DcR3）竞争 TL1A 结合并抑制功能信号。本篇综述重点介绍 TL1A/DR3/DcR3 细胞因子系统在炎症性肠病（IBD）中的作用。
TL1A 可能通过作用于 DR3 表达的 CD4+CD161+淋巴细胞诱导 IBD 中的 IFN-γ 介导和 IL-17 介导的促炎途径，这些细胞在炎症性肠黏膜中大量富集。此外，TL1A/DR3 信号导致 Treg 池的扩张，同时伴随其抑制功能的短暂抑制。转基因小鼠中 TL1A 的组成型表达与小肠炎症相关，在自发性和致结肠炎条件下均伴有结肠纤维化。最近的人类研究表明，活性 IBD 患者的循环系统中存在可溶性 TL1A 和 DcR3，并在成功抗炎治疗后下降。
TL1A/DR3 相互作用可能参与慢性肠道炎症的发病机制，并为溃疡性结肠炎和克罗恩病患者提供新的治疗靶点。
