Microglial IRF5-IRF4 regulatory axis regulates neuroinflammation after cerebral ischemia and impacts stroke outcomes

Significance Cerebral ischemia is a powerful stimulus to induce pro- and antiinflammatory responses, with the former destructive and the latter reparative in the disease progress. Microglia, the resident immune cells in the brain, are the key cells in initiating and perpetuating the poststroke inflammation. If microglial activation after stroke can be controlled, the poststroke inflammation will be quenched and stroke outcomes improved. In this study, we identified a key determinant for microglial pro- and antiinflammatory activation, the IRF5-IRF4 regulatory axis. We demonstrated that the manipulation of the axis alters stroke outcomes. This is an important finding, as the IRF5-IRF4 regulatory axis potentially provides stroke scientists with a therapeutic target for the treatment of stroke.