The tumor necrosis factor-like cytokine 1A/death receptor 3 cytokine system in intestinal inflammation.

PURPOSE OF REVIEW

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).

RECENT FINDINGS

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.

SUMMARY

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.