title: Functional signaling of membrane-bound TL1A induces IFN-gamma expression.
abstract: 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-gamma 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-gamma secretion enhancement. Anti-TL1A antibodies designed to treat immune diseases should be verified to block both endogenous TL1A forms.
authors.affiliation: Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Biener-Ramanujan
authors.forename: Rivkah
authors.initials: R
authors.lastname: Gonsky
authors.forename: Brian
authors.initials: B
authors.lastname: Ko
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
mesh_terms: D022082:Cellular Structures / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D020382:Interleukin-18; D053219:Receptors, Tumor Necrosis Factor, Member 25; D018664:Interleukin-12