title: Thioredoxin binding protein 2 modulates natural killer T cell-dependent innate immunity in the liver: possible link to lipid metabolism.
abstract: Thioredoxin binding protein 2 (TBP2) plays a regulatory role in lipid metabolism and immune regulation. We previously reported the effect of TBP2 loss-of-function on lipid metabolism using TBP2 knockout (TBP2KO) mice. In this study, we employed TBP2 transgenic (TBP2TG) mice to analyze the in vivo effect of TBP2 gain-of-function. We revealed a decrease in the percentage of hepatic natural killer T (NKT) cells in TBP2KO mice and an increase in the percentage of hepatic NKT cells in TBP2TG mice. The TBP2KO mice were resistant to concanavalin A (ConA)-induced hepatitis, but they were highly susceptible to other types of hepatitis. TBP2 modulates lipid metabolism as well as NKT cell activity. Moreover, TBP2 expression was increased significantly in klotho-deficient mice, which exhibit a syndrome resembling aging human phenotypes. TBP2 may play multiple roles in lipid metabolism, innate immunity, and aging.
authors.affiliation: Thioredoxin Project, Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okuyama
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshida
authors.forename: Aoi
authors.initials: A
authors.lastname: Son
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Oka
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Rika
authors.initials: R
authors.lastname: Nakayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masutani
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yo-ichi
authors.initials: Y
authors.lastname: Nabeshima
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology; D003208:Concanavalin A; D005260:Female; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007328:Insulin / Q000378:metabolism; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000276:immunology; D000090265:Klotho Proteins; D050356:Lipid Metabolism; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D055610:Antigens, CD1d; D002352:Carrier Proteins; C508022:Il2rb protein, mouse; D007328:Insulin; D053646:Interleukin-2 Receptor beta Subunit; C486715:TXNIP protein, human; C445672:Txnip protein, mouse; D003208:Concanavalin A; D013879:Thioredoxins; D005966:Glucuronidase; D000090265:Klotho Proteins