The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging.
J Clin Invest
; 131(4)2021 02 15.
Article
en En
| MEDLINE
| ID: mdl-33586677
Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Envejecimiento
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Macrófagos Alveolares
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Microambiente Celular
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Pulmón
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Clin Invest
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos