Model of the ROS- and ataxia-telangiectasia mutated (ATM)–mediated repression of neutrophil inflammatory responses. Following stimulation, neutrophils generate a burst of ROS that activates ATM-dependent DNA damage signaling to suppress cytokine production and induce apoptosis. Deficiency in ROS production or in ATM disables this inhibitory circuit, resulting in overproduction of cytokines, enhanced survival of activated neutrophils, and hyperinflammation. The MRN complex is composed of Mre11/Rad50/Nbs1 proteins. “P” represents phosphorylation of ATM, which is the active form of the kinase. AT, ataxia-telangiectasia; CGD, chronic granulomatous disease. See supplemental Figure 12 in the article by Harbort et al, available on the Blood Web site.