biostudies-literatureHonda AAmerican Heart AssociationHHS | National Institutes of HealthNCATS NIH HHSNIAID NIH HHSNHLBI NIH HHSHHS | NIH | National Institute of Allergy and Infectious DiseasesHHS | NIH | National Heart, Lung, and Blood Institute1947-1959https://www.ebi.ac.uk/biostudies/studies/S-EPMC9012679biostudies-literatureUnknown208(8)Immaturity of alveolar macrophages (AMs) around birth contributes to the susceptibility of newborns to lung disease. However, the molecular features differentiating neonatal and mature, adult AMs are poorly understood. In this study, we identify the unique transcriptomes and enhancer landscapes of neonatal and adult AMs in mice. Although the core AM signature was similar, murine adult AMs expressed higher levels of genes involved in lipid metabolism, whereas neonatal AMs expressed a largely proinflammatory gene profile. Open enhancer regions identified by an assay for transposase-accessible chromatin followed by high-throughput sequencing (ATAC-seq) contained motifs for nuclear receptors, MITF, and STAT in adult AMs and AP-1 and NF-κB in neonatal AMs. Intranasal LPS activated a similar innJournal of immunology (Baltimore, Md. : 1950)The Lung Microenvironment Instructs Gene Transcription in Neonatal and Adult Alveolar Macrophages.PMC9012679HL146066UL1TR001442UL1 TR001442HL143256HL147835AI036214HL148867HL126703U01 HL148867R01 HL143256P30 AI036214HL140198F31 HL146066R01 HL126703P01 HL147835K08 HL140198Nasamran CASajti EHonda ASekiya NMLund SJLakhdari OButcher LDFisch KMSakai MGlass CKRambaldo TCPrince LSHoeksema MAfalseThe Lung Microenvironment Instructs Gene Transcription in Neonatal and Adult Alveolar Macrophages.Immaturity of alveolar macrophages (AMs) around birth contributes to the susceptibility of newborns to lung disease. However, the molecular features differentiating neonatal and mature, adult AMs are poorly understood. In this study, we identify the unique transcriptomes and enhancer landscapes of neonatal and adult AMs in mice. Although the core AM signature was similar, murine adult AMs expressed higher levels of genes involved in lipid metabolism, whereas neonatal AMs expressed a largely proinflammatory gene profile. Open enhancer regions identified by an assay for transposase-accessible chromatin followed by high-throughput sequencing (ATAC-seq) contained motifs for nuclear receptors, MITF, and STAT in adult AMs and AP-1 and NF-κB in neonatal AMs. Intranasal LPS activated a similar inn2022-01-01T00:00:00Z2022 Apr2025-04-21T22:51:53.785Z2025-04-05T18:59:54.906ZS-EPMC90126793535461210.4049/jimmunol.2101192