IRF3 and IRF7 contribute to diesel exhaust particles‐induced pulmonary inflammation by mediating mTORC1 activation and restraining autophagy in mice

Exposure to diesel exhaust particles (DEPs) is associated with acute inflammatory responses in the lung and exacerbation of respiratory diseases. However, the mechanism by which DEPs trigger the inflammatory responses remains unclear. Here, we demonstrated that the IFN response factors IRF3 and IRF7 played pivotal roles in DEP‐induced pulmonary inflammation. DEPs could not directly induce inflammatory cytokine expression in mouse cells, whereas DEPs triggered autophagy both in vitro and in vivo. The DEP‐induced autophagy was augmented in the absence of IRF3 and IRF7, but not in the absence of IFNAR. The expression of Raptor was induced by IRF3 and IRF7 in response to DEPs treatment. Furthermore, administration of the mechanistic target of rapamycin (mTOR) inhibitor alleviated the inflammatory responses in the lung during DEP exposure. Our findings define an IFNAR‐independent role of increased autophagy in the absence of IRF3 and IRF7 during pulmonary DEP exposure, and provide the basis to develop new therapeutic approaches to counteract the adverse effects of DEPs and possibly other ambient particulate matters. IRF3 and IRF7 negatively regulate autophagy through inducing mTORC1 activity upon diesel exhaust particles exposure, which is not dependent on IFNAR signaling. The increased autophagy in the absence of IRF3 and IRF7 significantly attenuates the diesel exhaust particles induced pulmonary inflammation in mice.