IL-36 receptor deletion aggravates lung injury and mortality in experimental murine sepsis through epithelial
Inflammation resolution is critical for sepsis induced acute lung injury (ALI) recovery. Interleukin-36 receptor (IL-36R) is a potent anti-inflammatory factor. However, its role in ALI resolution remains unclear. We investigated the effects of IL-36R during the ALI resolution process in a murine cecal ligation and puncture (CLP)-induced ALI model. Knockout IL-36R signaling aggravates CLP-induced lung injury, as manifested by elevated bacterial load and increased neutrophils recruitment to the lung. Thereafter, we used IL-36R knockout mice to discern the source cell of IL-36R during ALI. We found that IL-36R is predominantly generated by epithelial cells during the ALI process. Furthermore, we sorted lung epithelial cells on the ALI process. IL-36R-specific loss in epithelial cells leads to apoptosis through NF-?B pathway. Together, our findings identify molecules that are likely involved in sepsis induced lung injury that may inform biomarker and therapeutic development. Overall design: On the third day of CLP, total RNA was extracted from the lung epithelial cells of 6 mice which were sepsis induced acute lung injury. Three of the mice knockout IL-36R while the other three were wild type mice. Subsequently, RNA-seq analysis was performed to examine gene expression in the lung epithelial cells.