STING-deficiency in lung resident mesenchymal stromal cells contributes to the alleviation of LPS-induced lung injury

Abstract

Acute respiratory distress syndrome (ARDS) is characterized by acute diffuse inflammatory lung injury with a high mortality rate. Mesenchymal stromal cells (MSC) are pluripotent adult cells that can be extracted from a variety of tissues, including the lung. Lung-resident MSC (LR-MSC) located around vascular vessels and act as important regulators of lung homeostasis, regulating the balance between lung injury and repair processes. LR-MSC support the integrity of lung tissue by modulating immune responses and releasing trophic factors. Studies have reported that the STING pathway is involved in the progression of lung injury inflammation, but the specific mechanism is unclear. In this study, we found that STING deficiency could ameliorate lipopolysaccharides (LPS)-induced acute lung injury, STING knockout (STING KO) LR-MSC had an enhanced treatment effect on acute lung injury. STING depletion protected LR-MSC from LPS-induced apoptosis. RNA-sequencing and Western blot results showed that STING KO LR-MSC expressed higher levels of MSC immunoregulatory molecules, such as Igfbp4, Icam1, Hgf and Cox2, than WT LR-MSC. This study highlights that LR-MSC have a therapeutic role in acute lung injury, and we demonstrate that STING deficiency can enhance the immunomodulatory function of LR-MSC in controlling lung inflammation. Thus, STING can be used as an intervention target to enhance the therapeutic effect of MSC.

Keywords: Acute lung injury; Acute respiratory distress syndrome; Mesenchymal stromal cells; STING.