Protective role of ILC2 in sepsis-induced acute lung injury

Abstract

Abstract Objective Group 2 innate lymphoid cells (ILC2), a recently identified population of innate immune cells, were suggested to be protective in infection. However, the underlying mechanism remains unknown. The current study aimed to determine the protective role of ILC2 in sepsis-induced acute lung inflammation and the underlying mechanism. Methods WT and IL-33 knockout mice were subjected to cecal ligation and puncture (CLP) to induce sepsis. The number of ILC2 and the concentration of cytokines including IL-4, IL-9 and IL-13 in the lung tissue were measured by flow cytometry and ELISA, respectively, at different time after CLP. In the in vitro studies, lung-derived ILC2 were co-cultured with mouse lung endothelial cells (LEC) and macrophages (MΦ), respectively, and challenged with LPS and/or TNF-α for up to 48 h. The LEC apoptosis and the ability of MΦ phagocytosis of bacteria were then detected by confocal fluorescence microscopy. Results Sepsis induced IL-33-dependent recruitment of ILC2 in the lung after CLP. The levels of ILC2-derived IL-9 and IL-13 significantly increased in the lung tissue of WT septic mice and in the supernatant of cultured ILC2 after LPS stimulation. IL-9 protects LPS/TNFα-induced LEC apoptosis, whereas, IL-13 decreased MΦ apoptosis in response to LPS/TNF-α. In addition, both IL-9 and IL-13 promote MΦ phagocytosis of bacteria. Conclusions IL-33-mediated ILC2 recruitment in the lung following sepsis protects lung injury through reducing apoptosis of LEC and MΦ and promotes bacteria clearance by MΦ. Increasing ILC2 and/or ILC2-derived cytokines in the lung may present a new therapeutic strategy for acute lung injury in sepsis.