Monocytes on the move: from pulmonary checkpoint to tissue fate

The pulmonary circulation is one of the largest endothelial interfaces in the body and, beyond gas exchange, it has been proposed as a site of neutrophil de-priming,1 a reservoir for platelet biogenesis2 and, as the study by Farahi and colleagues elegantly supports, an active participant in monocyte trafficking.3 The study invites further questions: why are monocytes retained in the lung? Where do they go when they leave? What happens when they get there?

In the past decade, deuterium-labelling studies have established a developmental continuum4 in which CD14⁺CD16^– (classical) monocytes emerge from the bone marrow, transition to CD14⁺CD16⁺ (intermediate) monocytes and finally mature into longer-lived CD14^loCD16⁺ (non-classical) monocytes that patrol the endothelium.5 From the circulation, monocytes may enter tissues to become monocyte-derived macrophages (MDMs). Single-cell and spatial transcriptomic approaches have revealed striking heterogeneity within each subset6 and enabled increasingly sophisticated…