[PDF][PDF] The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases

F Meylan, TS Davidson, E Kahle, M Kinder, K Acharya… - Immunity, 2008 - cell.com
F Meylan, TS Davidson, E Kahle, M Kinder, K Acharya, D Jankovic, V Bundoc, M Hodges…
Immunity, 2008cell.com
Summary 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 …
Summary
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, and cytokine production in Experimental Autoimmune Encephalomyelitis (EAE) and allergic lung inflammation, disease models that depend on distinct effector T cell subsets. DR3 could be an attractive therapeutic target for T cell-mediated autoimmune and allergic diseases.
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