Ability of IDO To Attenuate Liver Injury in alpha-Galactosylceramide-Induced Hepatitis Model

作者：Ito Hiroyasu^*; Hoshi Masato; Ohtaki Hirofumi; Taguchi Ayako; Ando Kazuki; Ishikawa Tetsuya; Osawa Yosuke; Hara Akira; Moriwaki Hisataka; Saito Kuniaki; Seishima Mitsuru

来源：The Journal of Immunology, 2010, 185(8): 4554-4560.

DOI：10.4049/jimmunol.0904173

IDO converts tryptophan to L-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, we examined the effect of IDO in alpha-galactosylceramide (alpha-GalCer)-induced hepatitis. The increase in IDO expression in the liver of wild-type (WT) mice administered alpha-GalCer was confirmed by real-time PCR, Western blotting, and IDO immunohistochemical analysis. The serum alanine aminotransferase levels in IDO-knockout (KO) mice after alpha-GalCer injection significantly increased compared with those in WT mice. 1-Methyl-D-tryptophan also exacerbated liver injury in this murine hepatitis model. In alpha-GalCer-induced hepatitis models, TNF-alpha is critical in the development of liver injury. The mRNA expression and protein level of TNF-alpha in the liver from IDO-KO mice were more enhanced compared with those in WT mice. The phenotypes of intrahepatic lymphocytes from WT mice and IDO-KO mice treated with alpha-GalCer were analyzed by flow cytometry, and the numbers of CD49b(+) and CD11b(+) cells were found to have increased in IDO-KO mice. Moreover, as a result of the increase in the number of NK cells and macrophages in the liver of IDO-KO mice injected with alpha-GalCer, TNF-alpha secretion in these mice was greater than that in WT mice. Deficiency of IDO exacerbated liver injury in alpha-GalCer-induced hepatitis. IDO induced by proinflammatory cytokines may decrease the number of TNF-alpha-producing immune cells in the liver. Thus, IDO may suppress overactive immune response in the alpha-GalCer-induced hepatitis model. The Journal of Immunology, 2010, 185: 4554-4560.

• 出版日期2010-10-15