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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.

Authors: Byrne AJ, Powell JE, OSullivan BJ, Ogger PP, Hoffland A, Cook J, Bonner KL, Hewitt RJ, Wolf S, Ghai P, Walker SA, Lukowski SW, Molyneaux PL, Saglani S, Chambers DC, Maher TM, Lloyd CM.
Journal: J Exp Med. 2020 Mar 2;217(3):e20191236
Year: 2020
PubMed: Find in PubMed