AI Article Synopsis
- The major histocompatibility complex (MHC) links innate and acquired immunity, and the role of the immunoresponsive gene 1 (IRG1) in innate immunity, particularly in reactive oxygen species (ROS) and inflammation, is significant but not fully understood in antigen presentation.
- Overexpressing IRG1 in macrophages was found to increase the level of MHC class I, while not affecting MHC class II, and promoted transporter proteins associated with antigen processing like TAP1 and PSMB9, influenced by ROS levels.
- The study confirmed that IRG1 enhances ROS production through the pentose phosphate pathway, and inhibition of ROS reduced MHC I expression, indicating that IRG1 modulates immune responses through the
Article 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.
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| http://dx.doi.org/10.1016/j.intimp.2017.04.012 | DOI Listing |
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