Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice

Abstract

Retinoids are potent transcriptional regulators that act in regulating cell proliferation, differentiation, and other cellular processes. We carried out studies in male mice to establish the importance of local cellular retinoid stores within the lung alveolus for maintaining its health in the face of an acute inflammatory challenge induced by intranasal instillation of lipopolysaccharide. We also undertook single cell RNA sequencing and bioinformatic analyses to identify roles for different alveolar cell populations involved in mediating these retinoid-dependent responses. Here we show that local retinoid stores and uncompromised metabolism and signaling within the lung are required to lessen the severity of an acute inflammatory challenge. Unexpectedly, our data also establish that alveolar cells other than lipofibroblasts, specifically microvascular endothelial and alveolar epithelial cells, are able to take up lipoprotein-transported retinoid and to accumulate cellular retinoid stores that are directly used to respond to an acute inflammatory challenge.

Retinoids can act as transcriptional regulators to regulate cell proliferation, differentiation, and other processes. Here, the authors show that uncompromised vitamin A (retinoid) metabolism and signaling in alveolar lipofibroblasts, endothelial and epithelial cells are required to lessen the severity of an acute inflammatory challenge in adult mouse lungs.