Analysis of therapeutic potential of preclinical models based on DR3/TL1A pathway modulation (Review).

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.