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Dynamics of human monocytes and airway macrophages during healthy aging and after transplant

Abstract

The ontogeny of airway macrophages (AMs) in human lung and their contribution to disease are poorly mapped out. In mice, aging is associated with an increasing proportion of peripherally, as opposed to perinatally derived AMs. We sought to understand AM ontogeny in human lung during healthy aging and after transplant. We characterized monocyte/macrophage populations from the peripheral blood and airways of healthy volunteers across infancy/childhood (2-12 yr), maturity (20-50 yr), and older adulthood (>50 yr). Single-cell RNA sequencing (scRNA-seq) was performed on airway inflammatory cells isolated from sex-mismatched lung transplant recipients. During healthy aging, the proportions of blood bronchoalveolar lavage (BAL) classical monocytes peak in adulthood and decline in older adults. scRNA-seq of BAL cells from lung transplant recipients indicates that after transplant, the majority of AMs are recipient derived. These data show that during aging, the peripheral monocyte phenotype is consistent with that found in the airways and, furthermore, that the majority of human AMs after transplant are derived from circulating monocytes.

Type Journal
ISBN 1540-9538 (Electronic) 0022-1007 (Linking)
Authors Byrne, A. J.; Powell, J. E.; O'Sullivan, B. J.; Ogger, P. P.; Hoffland, A.; Cook, J.; Bonner, K. L.; Hewitt, R. J.; Wolf, S.; Ghai, P.; Walker, S. A.; Lukowski, S. W.; Molyneaux, P. L.; Saglani, S.; Chambers, D. C.; Maher, T. M.; Lloyd, C. M.
Responsible Garvan Author A/Prof Joseph Powell
Publisher Name JOURNAL OF EXPERIMENTAL MEDICINE
Published Date 2020-03-31
Published Volume 217
Published Issue 3
Published Pages e20191236
Status Published in-print
DOI 10.1084/jem.20191236
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/31917836