NLRP3 regulates macrophage function by M-CSF/M-CSFR signaling in acute radiation-induced lung injury

Alveolar macrophages are the most abundant macrophages in the healthy lungs and are important players in maintaining lung homeostasis as well as orchestrating tissue repair after injury. Many studies have proved that the initiation, development and progression of acute radiation-induced lung injury are associated with alveolar macrophages. However, lung-associated macrophages function and developmental processes in acute radiation-reduced lung injury remain elusive. To investigate the role of NLRP3 in radiation-reduced lung injury, we established wild-type and NLRP3^-/- mice models, and we found that the extent of pneumonia reduced in NLRP3^-/- IR group. In in vivo experiments, we observed a decrease in the number of macrophages in NLRP3^-/- group. At the same time, in in vitro experiments we have found that macrophages are more easily polarized toward the M2 after radiation in NLRP3^-/- group compared with the control group. Our findings reveal that NLRP3 affects the differentiation and chemotaxis of alveolar macrophages through M-CSF/M-CSFR signalling at the onset of radiation-induced lung injury.