Human airspace macrophage signatures are conserved during sterile lung injury and repair
Abstract
Rationale: Airspace macrophages (AM) are implicated in both persistent inflammation and tissue repair following acute lung injury. Distinct subsets of AM are associated with lung pathology in humans, but whether unique AM signatures are specific to disease states or represent a conserved response to lung inflammation is unknown.
Objectives: We sought to test the hypothesis that conserved subsets of inflammatory and reparative AM could be identified by transcriptional programming in a human model of self-resolving acute lung injury.
Methods: A total of 15 participants underwent BAL before and at a pre-assigned time point after endobronchial exposure to bacterial endotoxin. Bronchoalveolar lavage cells were subjected to single cell RNA sequencing, and longitudinal assessment of AM programming during resolution of inflammation and lung repair was performed.
Measurements and Main Results: We identify transcriptionally distinct subsets of tissue resident and recruited AM present at all time points, in all participants. Two recruited AM populations increase following inflammation: one that aligns with classical monocytes and one with interstitial macrophages (IAM). Airspace macrophage subsets display unique patterns of gene expression throughout the time course. Comparison of subset-specific markers to those identified in disease states reveals that IAM express many so-called pathogenic markers during normal lung repair.
Conclusions: By applying a uniform inflammatory stimulus to healthy adults and examining BAL cells obtained at precise time points thereafter, we construct a time-resolved kinetic of AM transcriptional programming during typical lung repair. Our data demonstrate that IAM share transcriptional similarity to AM identified in disease states and suggest they may reflect a conserved cellular response to tissue injury.
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BibTeX
@article{moore2026human,
title = {{Human airspace macrophage signatures are conserved during sterile lung injury and repair}},
author = {Camille M Moore and Shannon A McManus and Elizabeth A Wynn and Jazalle D McClendon and William J Janssen and Kara J Mould},
journal = {American Journal of Respiratory and Critical Care Medicine},
year = {2026},
month = sep,
doi = {10.1093/ajrccm/aamag327},
url = {https://doi.org/10.1093/ajrccm/aamag327},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Human airspace macrophage signatures are conserved during sterile lung injury and repair
AU - Camille M Moore
AU - Shannon A McManus
AU - Elizabeth A Wynn
AU - Jazalle D McClendon
AU - William J Janssen
AU - Kara J Mould
PY - 2026
DA - 2026/09/12
JO - American Journal of Respiratory and Critical Care Medicine
DO - 10.1093/ajrccm/aamag327
UR - https://doi.org/10.1093/ajrccm/aamag327
AB - Rationale: Airspace macrophages (AM) are implicated in both persistent inflammation and tissue repair following acute lung injury. Distinct subsets of AM are associated with lung pathology in humans, but whether unique AM signatures are specific to disease states or represent a conserved response to lung inflammation is unknown. Objectives: We sought to test the hypothesis that conserved subsets of inflammatory and reparative AM could be identified by transcriptional programming in a human model of self-resolving acute lung injury. Methods: A total of 15 participants underwent BAL before and at a pre-assigned time point after endobronchial exposure to bacterial endotoxin. Bronchoalveolar lavage cells were subjected to single cell RNA sequencing, and longitudinal assessment of AM programming during resolution of inflammation and lung repair was performed. Measurements and Main Results: We identify transcriptionally distinct subsets of tissue resident and recruited AM present at all time points, in all participants. Two recruited AM populations increase following inflammation: one that aligns with classical monocytes and one with interstitial macrophages (IAM). Airspace macrophage subsets display unique patterns of gene expression throughout the time course. Comparison of subset-specific markers to those identified in disease states reveals that IAM express many so-called pathogenic markers during normal lung repair. Conclusions: By applying a uniform inflammatory stimulus to healthy adults and examining BAL cells obtained at precise time points thereafter, we construct a time-resolved kinetic of AM transcriptional programming during typical lung repair. Our data demonstrate that IAM share transcriptional similarity to AM identified in disease states and suggest they may reflect a conserved cellular response to tissue injury.
SN - 1073-449X
SN - 1535-4970
ER -