Functional signaling of membrane‐bound TL1A induces IFN‐γ expression

TL1A, a TNF member implicated in autoimmune diseases, is a transmembrane protein that is processed to release soluble TL1A (TL1A‐S). TL1A‐S induces a Th1 response, although the functional significance of membrane‐bound TL1A (TL1A‐M) remains unknown. We generated TL1A‐M expression in HEK‐293 cells capable of binding DR3‐Fc. Co‐incubating IL‐12/IL‐18‐primed CD4 + T cells with HEK‐293 cells expressing TL1A‐M induced 3‐fold increase in IFN‐γ that was blocked by anti‐TL1A Ab. These results demonstrate that TL1A‐M can bind death domain receptor 3 (DR3) through cell–cell contact to induce downstream IFN‐γ secretion enhancement. Anti‐TL1A antibodies designed to treat immune diseases should be verified to block both endogenous TL1A forms.