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- W4313373130 abstract "Abstract Alveolar macrophages (AMs) perform specialized functions in the lung including protection against inhaled microbes and repair following injury. Neonates are particularly susceptible to lung infection and injury, suggesting immaturity of AM function. In mice, AMs differentiate from fetal myeloid precursors within the first week following birth. To measure the molecular and functional differences between neonatal and adult AMs, we performed RNA-seq and ATAC-seq on sorted AMs. Based on RNA-seq data, adult AMs expressed higher levels of genes associated with fatty acid metabolism (Fabp1 and Abcg1), while neonatal AMs expressed higher levels of proinflammatory genes (including Il1b, Il6, Tnf, and S100a8). Consistent with higher proinflammatory gene expression in neonatal AMs, ATAC-seq revealed enrichment of accessible AP1, NF-kB, and IRF binding motifs. In contrast, adult AMs contained open chromatin enriched in motifs for KLF, AR, and STAT. To test if these differences contributed to differential innate immune function, we treated both neonatal and adult mice in vivo with inhaled LPS. LPS-exposed AMs demonstrated robust innate immune responses in both neonatal and adult mice. Interestingly, many of the LPS-induced genes in neonatal AMs had higher basal levels of expression, suggesting constitutive innate immune activation in the neonatal lung. These differences appeared to be driven by the lung microenvironment, as isolating and culturing AMs resulted in rapid loss of differences in gene expression between neonatal and adult cells. Our data therefore suggest the developing environment of the neonatal lung drives unique molecular and functional differences in AM mediated innate immunity." @default.
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- W4313373130 date "2020-05-01" @default.
- W4313373130 modified "2023-10-02" @default.
- W4313373130 title "Distinct Changes in the Chromatin Landscape Regulate Maturation of the Alveolar Macrophage Immune Response In Vivo" @default.
- W4313373130 doi "https://doi.org/10.4049/jimmunol.204.supp.152.4" @default.
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