biostudies-literatureMeylan FIntramural NIH HHSMedical Research Council79-89https://www.ebi.ac.uk/biostudies/studies/S-EPMC2760084biostudies-literatureUnknown29(1)DR3 (TRAMP, LARD, WSL-1, TNFRSF25) is a death-domain-containing tumor necrosis factor (TNF)-family receptor primarily expressed on T cells. TL1A, the TNF-family ligand for DR3, can costimulate T cells, but the physiological function of TL1A-DR3 interactions in immune responses is not known. Using DR3-deficient mice, we identified DR3 as the receptor responsible for TL1A-induced T cell costimulation and dendritic cells as the likely source for TL1A during T cell activation. Despite its role in costimulation, DR3 was not required for in vivo T cell priming, for polarization into T helper 1 (Th1), Th2, or Th17 effector cell subtypes, or for effective control of infection with Toxoplasma gondii. Instead, DR3 expression was required on T cells for immunopathology, local T cell accumulation, andImmunityThe TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases.PMC2760084G0300180(65735)G0500617(74644)G0500617Z01 AR041174-01G0300180Kinder MBundoc VShevach EMDavidson TSKahle EMeylan FJankovic DSiegel RMWang ECAcharya KHodges MKeane-Myers AfalseThe TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases.DR3 (TRAMP, LARD, WSL-1, TNFRSF25) is a death-domain-containing tumor necrosis factor (TNF)-family receptor primarily expressed on T cells. TL1A, the TNF-family ligand for DR3, can costimulate T cells, but the physiological function of TL1A-DR3 interactions in immune responses is not known. Using DR3-deficient mice, we identified DR3 as the receptor responsible for TL1A-induced T cell costimulation and dendritic cells as the likely source for TL1A during T cell activation. Despite its role in costimulation, DR3 was not required for in vivo T cell priming, for polarization into T helper 1 (Th1), Th2, or Th17 effector cell subtypes, or for effective control of infection with Toxoplasma gondii. Instead, DR3 expression was required on T cells for immunopathology, local T cell accumulation, and2008-01-01T00:00:00Z2008 Jul2025-04-03T23:19:02.408Z2019-03-27T00:25:46ZS-EPMC27600841857144310.1016/j.immuni.2008.04.021