title: Role of TNFR-related 2 mediated immune responses in dextran sulfate sodium-induced inflammatory bowel disease.
abstract: Previous work has suggested that the LIGHT-TR2 costimulatory pathway plays a role in the acute and chronic stages of dextran sulfate sodium (DSS)-induced colitis [Steinberg et al. (2008); Wang et al. (2005)]. To clarify the role of TNFR-related 2 (TR2) signaling in the maintenance of intestinal homeostasis, we generated a TR2 knock-out (KO) mouse. Using DSS to induce colitis, we compared the colitic symptoms and pathological changes in wild type (WT) and TR2 KO mice, and the production of cytokines by the diseased colons. We also studied the role of TR2 in suppressing innate and adaptive immunity in the DSS model. TR2 deficient mice were characterized by reduced symptoms of intestinal inflammation compared with wild-type mice, and reduced production of cytokines. We therefore generated a monoclonal antibody against mouse TR2 which was specific to TR2 and capable of blocking TR2 signals. With this antibody, we demonstrated that antagonizing TR2 during the development of DSS-induced colitis reduced the symptoms of inflammation. Our findings suggest that TR2 is an important mediator in colitis, and may serve as a therapeutic target in inflammatory bowel disease.
authors.affiliation: Department of Biological Science, University of Ulsan, Ulsan, Korea.
authors.forename: Woon-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Jin-Soo
authors.initials: JS
authors.lastname: Park
authors.forename: Ok-Ju
authors.initials: OJ
authors.lastname: Sul
authors.forename: Jae-Hee
authors.initials: JH
authors.lastname: Seo
authors.forename: Byum-Kyu
authors.initials: BK
authors.lastname: Choi
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Anne M
authors.initials: AM
authors.lastname: Latour
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Koller
authors.forename: Byoung S
authors.initials: BS
authors.lastname: Kwon
authors.forename: Choon-Soo
authors.initials: CS
authors.lastname: Jeong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000150:complications / Q000276:immunology / Q000473:pathology; D007109:Immunity / Q000187:drug effects / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D018836:Inflammation Mediators; D047889:Receptors, Tumor Necrosis Factor, Type II; D016264:Dextran Sulfate