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

• Published in: International immunopharmacology 2017-07, Vol.48, p.76-83
• Main Authors: Liu, Xing, Wu, Xiao-Pan, Zhu, Xi-Lin, Li, Tao, Liu, Ying
• Format: Article
• Language: English
• Subjects: Antigen presentation; Antigen processing; Antigens; ATP-Binding Cassette Sub-Family B Member 2 - genetics; Cell Line; Cysteine Endopeptidases - genetics; Glucose 6 phosphate dehydrogenase; Glucosephosphate dehydrogenase; Glycometabolism; Histocompatibility Antigens Class I - metabolism; Humans; Immune system; Immunity; Immunoglobulin G - metabolism; Inflammation; Innate immunity; IRG1; Macrophages; Macrophages - metabolism; Major histocompatibility complex; NAD(P)H oxidase; NADPH Oxidase 1; NADPH Oxidases - metabolism; Oxidase; Pentose; Pentose phosphate pathway; Phosphates; Phosphorylation; Proteins; Proteins - genetics; Proteins - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; RNA, Messenger - metabolism; ROS; Stat1 protein; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; TAP
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2017.04.012

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. •Immunoresponsive gene 1 (IRG1) regulates MHC I level through ROS.•IRG1 increases ROS level by promoting pentose phosphate pathway and NOX.•ROS promotes TAP1 and PSMB9 expression by activated STAT1/3.