Group 2 innate lymphoid cells derived IL-9 reduces macrophage apoptosis and attenuates acute lung injury in sepsis.

Abstract

Background: Group 2 innate lymphoid cells (ILC2) are the main group of tissue-resident ILCs in the lungs, which protect airway barrier integrity following infection. Macrophages are integral to the regulation of immune homeostasis in sepsis. However, the relationship between ILC2 and macrophages in the context of sepsis induced acute lung injury remains uncertain.

Methods: The sepsis was conducted by cecal ligation and puncture (CLP) model in Wild Type (WT) mice and ILC2 depleted mice. Septic mice were injected intratracheally IL-9, and the frequency and markers expression of ILC2 and macrophage were measured by Flow cytometry and CyTOF. The lung injury was conducted with pathological analysis. In vitro studies, MH-S cells were exposed to LPS with/without interleukin-9 (IL-9), and mTOR level and MH-S cells death were measured with western bloting or Flow cytometry.

Results: Sepsis induced the accumulation of ILCs and pulmonary macrophages in lungs. Furtherly, we revealed that ILC2 and CD45⁺F4/80⁺CD11c⁺ macrophages expanded during sepsis induced acute lung injury. Meanwhile, ILC2 depletion significantly enhanced macrophages expansion. In vivo and in vitro studies determined that pulmonary macrophage death followed by sepsis were protedced by IL-9, which was main secreted by ILC2 in lung. Furthermore, IL-9 significantly declined the expression of mTOR, and the presence of ILC2 or IL-9 reduced the expression of M1 markers (CD86 or MHC II).

Conclusions: IL-9 secreted by ILC2 has a protective role in sepsis induced lung injury by reducing macrophage apoptosis and M1 polarization via mTOR.