Cellular Reactive Oxygen Species Inhibit MPYS Induction of IFNβ

Many inflammatory diseases, as well as infections, are accompanied by elevation in cellular levels of Reactive Oxygen Species (ROS). Here we report that MPYS, a.k.a. STING, which was recently shown to mediate activation of IFN beta expression during infection, is a ROS sensor. ROS induce intermolecular disulfide bonds formation in MPYS homodimer and inhibit MPYS IFN beta stimulatory activity. Cys-64, -148, -292, -309 and the potential C(88)xxC(91) redox motif in MPYS are indispensable for IFN beta stimulation and IRF3 activation. Thus, our results identify a novel mechanism for ROS regulation of IFN beta stimulation.