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The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases.

ABSTRACT: 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.

SUBMITTER: Meylan F

PROVIDER: S-EPMC2760084 | biostudies-other | 2008 Jul

REPOSITORIES: biostudies-other

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The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases.

Meylan Françoise F Davidson Todd S TS Kahle Erin E Kinder Michelle M Acharya Krishika K Jankovic Dragana D Bundoc Virgilio V Hodges Marcus M Shevach Ethan M EM Keane-Myers Andrea A Wang Eddie C Y EC Siegel Richard M RM

Immunity 20080619 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 co ...[more]

PMID: 18571443

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The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases.

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The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases.

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