TY - JOUR
T1 - The Lung Microenvironment Instructs Gene Transcription in Neonatal and Adult Alveolar Macrophages
AU - Honda, Asami
AU - Hoeksema, Marten A.
AU - Sakai, Mashito
AU - Lund, Sean J.
AU - Lakhdari, Omar
AU - Butcher, Lindsay D.
AU - Rambaldo, Tara C.
AU - Sekiya, Neal M.
AU - Nasamran, Chanond A.
AU - Fisch, Kathleen M.
AU - Sajti, Eniko
AU - Glass, Christopher K.
AU - Prince, Lawrence S.
N1 - Funding Information: This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute Grants HL126703 (to L.S.P.), HL143256 (to L.S.P. and E.S.), HL146066 (to S.J.L.), HL148867 (to E.S.), HL140198 (to E.S.), and HL147835 (to C.K.G. and M.S.), and by an American Heart Association Fellowship (to M.A.H.). This work was performed with the support of the Flow Cytometry Core at the San Diego Center for AIDS Research (National Institute of Allergy and Infectious Diseases Grant Funding Information: This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute Grants HL126703 (to L.S.P.), HL143256 (to L.S.P. and E.S.), HL146066 (to S.J.L.), HL148867 (to E.S.), HL140198 (to E.S.), and HL147835 (to C.K.G. and M.S.), and by an American Heart Association Fellowship (to M.A.H.). This work was performed with the support of the Flow Cytometry Core at the San Diego Center for AIDS Research (National Institute of Allergy and Infectious Diseases Grant P30 AI036214), the VA San Diego Health Care System, and the San Diego Veterans Medical Research Foundation. The project was partially supported by National Institutes of Health Grant UL1TR001442 of the University of California, San Diego Clinical and Translational Science Award Program. Funding Information: P30 AI036214), the VA San Diego Health Care System, and the San Diego Veterans Medical Research Foundation. The project was partially supported by National Institutes of Health Grant UL1TR001442 of the University of California, San Diego Clinical and Translational Science Award Program. Publisher Copyright: Copyright © 2022 by The American Association of Immunologists, Inc. All rights reserved.
PY - 2022/4/15
Y1 - 2022/4/15
N2 - 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-kB in neonatal AMs. Intranasal LPS activated a similar innate immune response in both neonatal and adult mice, with higher basal expression of inflammatory genes in neonates. The lung microenvironment drove many of the distinguishing gene expression and open chromatin characteristics of neonatal and adult AMs. Neonatal mouse AMs retained high expression of some proinflammatory genes, suggesting that the differences in neonatal AMs result from both inherent cell properties and environmental influences.
AB - 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-kB in neonatal AMs. Intranasal LPS activated a similar innate immune response in both neonatal and adult mice, with higher basal expression of inflammatory genes in neonates. The lung microenvironment drove many of the distinguishing gene expression and open chromatin characteristics of neonatal and adult AMs. Neonatal mouse AMs retained high expression of some proinflammatory genes, suggesting that the differences in neonatal AMs result from both inherent cell properties and environmental influences.
UR - http://www.scopus.com/inward/record.url?scp=85128488706&partnerID=8YFLogxK
U2 - https://doi.org/10.4049/jimmunol.2101192
DO - https://doi.org/10.4049/jimmunol.2101192
M3 - Article
C2 - 35354612
SN - 0022-1767
VL - 208
SP - 1947
EP - 1959
JO - Journal of immunology (Baltimore, Md.
JF - Journal of immunology (Baltimore, Md.
IS - 8
ER -