J Immunol

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.F31 HL151199/HL/NHLBI NIH HHSUnited States/R01 DK100917/DK/NIDDK NIH HHSUnited States/T32 GM008646/GM/NIGMS NIH HHSUnited States/U01 IP000017/IP/NCIRD CDC HHSUnited States