Thioredoxin binding protein 2 modulates natural killer T cell-dependent innate immunity in the liver: possible link to lipid metabolism

Hiroaki Okuyama; Toru Yoshida; Aoi Son; Shin-ichi Oka; Dongmei Wang; Rika Nakayama; Hiroshi Masutani; Hajime Nakamura; Yo-ichi Nabeshima; Junji Yodoi

doi:10.1089/ars.2009.2691

Thioredoxin binding protein 2 modulates natural killer T cell-dependent innate immunity in the liver: possible link to lipid metabolism

Antioxid Redox Signal. 2009 Oct;11(10):2585-93. doi: 10.1089/ars.2009.2691.

Authors

Hiroaki Okuyama¹, Toru Yoshida, Aoi Son, Shin-ichi Oka, Dongmei Wang, Rika Nakayama, Hiroshi Masutani, Hajime Nakamura, Yo-ichi Nabeshima, Junji Yodoi

Affiliation

¹ Thioredoxin Project, Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.

PMID: 19619006
DOI: 10.1089/ars.2009.2691

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / physiology
Animals
Antigens, CD1d / genetics
Antigens, CD1d / immunology
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cells, Cultured
Chemical and Drug Induced Liver Injury / metabolism
Chemical and Drug Induced Liver Injury / pathology
Concanavalin A
Female
Glucuronidase / genetics
Glucuronidase / metabolism
Hepatocytes / cytology
Hepatocytes / metabolism
Humans
Immunity, Innate / immunology*
Insulin / metabolism
Interleukin-2 Receptor beta Subunit / genetics
Interleukin-2 Receptor beta Subunit / immunology
Klotho Proteins
Lipid Metabolism*
Liver / immunology*
Liver / pathology
Liver / physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Natural Killer T-Cells / cytology
Natural Killer T-Cells / immunology*
Thioredoxins / genetics
Thioredoxins / metabolism*

Substances

Antigens, CD1d
Carrier Proteins
Il2rb protein, mouse
Insulin
Interleukin-2 Receptor beta Subunit
TXNIP protein, human
Txnip protein, mouse
Concanavalin A
Thioredoxins
Glucuronidase
Klotho Proteins