Lung environment in healthy old age shapes the phenotype and CCR2-mediated recruitment of a subset of apoptotic, high-turnover alveolar macrophages
Abstract
Immune system changes with healthy aging lead to chronic systemic inflammation termed inflammaging, contributing to age-related pathologies. Alveolar macrophages (AMs) maintain lung homeostasis and health. The impact of inflammaging on AM populations requires further definition. Herein, we examined the effect of healthy old age on the phenotype and ontogeny of AMs from mice, non-human primates and humans. We identify three AM subpopulations in old age, including a CD11c ⁺ CD11b ⁺ population that increases more than 10-fold across mammalian species, leading to significant changes associated with heightened inflammation and immune dysregulation. RNA-seq analysis identifies distinct transcriptional AM subpopulation profiles. Experiments in mice reveal the importance of the alveolar environment in shaping AM phenotype and recruitment in healthy old age. The old age alveolar environment promotes phenotypic reprogramming of tissue-resident AMs (TRAMs) toward a CD11c ⁺ CD11b ⁺ state in addition to enhancing CCR2-dependent recruitment of monocyte-derived AMs, which are relatively short-lived and exhibit high turnover due to Fas-mediated apoptosis. These studies provide important insight regarding the impact of the alveolar environment in healthy old age on AM phenotype and function.
Related
- SEC31A promotes gastric cancer progression by inducing the PI3K/AKT/mTOR pathway and enhancing the CCL5-mediated M2 polarization and recruitment of tumor-associated macrophages
- Macrophages discriminate and sort pathogenic bacteria and apoptotic material during dual-target phagocytosis
- Anti-inflammatory macrophages limit endothelial inflammation and restrict neutrophil recruitment through Gas6/AXL signaling
- Bi-layered living cellular constructs promote recruitment and activation of an M2 macrophage phenotype
- Histone lactylation in fibroblast-like synoviocytes drives CXCL1-mediated immune cell recruitment in rheumatoid arthritis
BibTeX
@article{pahari2026lung,
title = {{Lung environment in healthy old age shapes the phenotype and CCR2-mediated recruitment of a subset of apoptotic, high-turnover alveolar macrophages}},
author = {Susanta Pahari and Miranda Lumbreras and Arkajyoti Paul and Abul Azad and Hao Zhang and Hong Cai and Zhao Lai and Diego Jose Maselli and Jay Peters and Jordi B. Torrelles and Joanne Turner and Florent Ginhoux and William P. Lafuse and Yufeng Wang and Eusondia Arnett and Larry S. Schlesinger},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78156-x},
url = {https://www.nature.com/articles/s41467-026-78156-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lung environment in healthy old age shapes the phenotype and CCR2-mediated recruitment of a subset of apoptotic, high-turnover alveolar macrophages
AU - Susanta Pahari
AU - Miranda Lumbreras
AU - Arkajyoti Paul
AU - Abul Azad
AU - Hao Zhang
AU - Hong Cai
AU - Zhao Lai
AU - Diego Jose Maselli
AU - Jay Peters
AU - Jordi B. Torrelles
AU - Joanne Turner
AU - Florent Ginhoux
AU - William P. Lafuse
AU - Yufeng Wang
AU - Eusondia Arnett
AU - Larry S. Schlesinger
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-78156-x
UR - https://www.nature.com/articles/s41467-026-78156-x
AB - Immune system changes with healthy aging lead to chronic systemic inflammation termed inflammaging, contributing to age-related pathologies. Alveolar macrophages (AMs) maintain lung homeostasis and health. The impact of inflammaging on AM populations requires further definition. Herein, we examined the effect of healthy old age on the phenotype and ontogeny of AMs from mice, non-human primates and humans. We identify three AM subpopulations in old age, including a CD11c ⁺ CD11b ⁺ population that increases more than 10-fold across mammalian species, leading to significant changes associated with heightened inflammation and immune dysregulation. RNA-seq analysis identifies distinct transcriptional AM subpopulation profiles. Experiments in mice reveal the importance of the alveolar environment in shaping AM phenotype and recruitment in healthy old age. The old age alveolar environment promotes phenotypic reprogramming of tissue-resident AMs (TRAMs) toward a CD11c ⁺ CD11b ⁺ state in addition to enhancing CCR2-dependent recruitment of monocyte-derived AMs, which are relatively short-lived and exhibit high turnover due to Fas-mediated apoptosis. These studies provide important insight regarding the impact of the alveolar environment in healthy old age on AM phenotype and function.
SN - 2041-1723
ER -