Functions to Regulate Inflammation in Alveolar Macrophages during Acute Lung Injury.

Our respiratory system is vital to protect us from the surrounding nonsterile environment; therefore, it is critical for a state of homeostasis to be maintained through a balance of inflammatory cues. Recent studies have shown that actively transcribed noncoding regions of the genome are emerging as key regulators of biological processes, including inflammation. is one such example of an inflammatory inducible long intergenic noncoding RNA functioning to fine-tune immune gene expression. Using bulk and single-cell RNA sequencing, in addition to FACS, we find that is most highly expressed in the lung and is most upregulated after LPS-induced lung injury (acute lung injury [ALI]) within alveolar macrophages, where it functions to regulate inflammation. We previously reported that functions to regulate its neighboring protein Ptgs2 in , and in this study, we use genetic mouse models to confirm its role in regulating gene expression more broadly in during ALI. Il6, Ccl3, and Ccl5 are dysregulated in the -deficient mice and can be rescued to wild type levels by crossing the deficient mice with our newly generated transgenic mice, confirming that this gene functions in Many genes are specifically regulated by within alveolar macrophages originating from the bone marrow because the phenotype can be reversed by transplantation of wild type bone marrow into the -deficient mice. In conclusion, we show that is a -acting long noncoding RNA that functions to regulate immune responses and maintain homeostasis within the lung at baseline and on LPS-induced ALI.