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Int Immunopharmacol. 2017 Jul;48:76-83. doi: 10.1016/j.intimp.2017.04.012. Epub 2017 May 5.

IRG1 increases MHC class I level in macrophages through STAT-TAP1 axis depending on NADPH oxidase mediated reactive oxygen species.

Author information

1
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
2
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China. Electronic address: liuyingpumc@yeah.net.

Abstract

The major histocompatibility complex (MHC) is the connection between innate immunity and acquired immune system. Recently, many studies reported that the immunoresponsive gene 1 (IRG1) play an important role on innate immunity including reactive oxygen species (ROS), antiviral effect and expression of inflammatory factors. However, the function of IRG1 in antigen presenting remains unclear. In this study, we found that overexpressed-IRG1 promoted MHC I level instead of MHC II in macrophages membrane. Besides, IRG1 increased expression of some transporter proteins associated with antigen processing involving TAP1, PSMB9 depending on ROS. By detecting the activation of glucose-6-phosphate dehydrogenase (G6PD), we confirmed that IRG1 could increase ROS level by promoting pentose phosphate pathway (PPP). DPI, an inhibitor of NADPH oxidase (NOX), also significant attenuated TAP1 and MHC I level in IRG1-overexpressed macrophages. Finally, results showed that phosphorylation of STAT1/3 involved in IRG1-mediated TAP1 and MHC I expression. In conclusion, IRG1 increased MHC class I level in macrophages through STAT1/3-TAP1 axis depending on PPP and NOX mediated ROS.

KEYWORDS:

Antigen presentation; Glycometabolism; IRG1; ROS; TAP

PMID:
28477473
DOI:
10.1016/j.intimp.2017.04.012
[Indexed for MEDLINE]

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