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

Meylan, Françoise, Davidson, Todd S., Kahle, Erin, Kinder, Michelle, Acharya, Krishika, Jankovic, Dragana, Bundoc, Virgilio, Hodges, Marcus, Shevach, Ethan M., Keane-Myers, Andrea, Wang, Edward Chung Yern and Siegel, Richard M. 2008. The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases. Immunity 29 (1) , pp. 79-89. 10.1016/j.immuni.2008.04.021

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Uncontrolled Keywords: molimmuno
Publisher: Elsevier
ISSN: 1074-7613
Last Modified: 04 Jun 2017 03:43
URI: http://orca.cf.ac.uk/id/eprint/25543

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