Thioredoxin binding protein 2 modulates natural killer T cell-dependent innate immunity in the liver: possible link to lipid metabolism.
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.
Okuyama
Hiroaki
H
Thioredoxin Project, Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
Yoshida
Toru
T
Son
Aoi
A
Oka
Shin-ichi
S
Wang
Dongmei
D
Nakayama
Rika
R
Masutani
Hiroshi
H
Nakamura
Hajime
H
Nabeshima
Yo-ichi
Y
Yodoi
Junji
J
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*
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