Tissue-resident macrophages can be derived from yolk-sac macrophages, fetal-liver monocytes or bone-marrow monocytes. In Immunity, van de Laar et al. use intranasal transfer of these precursor cells into neonatal Csf2rb−/− mice, which have empty alveolar-macrophage niches, to investigate their relative ability to colonize the niche and perform tissue-specific functions. When these progenitors are transferred together in equal ratios, fetal-liver monocytes preferentially (80%) reconstitute the alveolar-macrophage niche in the Csf2rb−/− hosts, possibly due to low expression of the receptor for the cytokine GM-CSF on yolk-sac macrophages and poor expression of proliferation-associated genes in bone-marrow monocytes. When transferred separately, all progenitor cells efficiently colonize the niche, acquire an alveolar-macrophage-specific profile with only limited gene-expression differences (7–12 genes) linked to precursor origin, and produce macrophages that are functionally equivalent. In contrast, mature peritoneal, colon and liver macrophages do not colonize this niche after transfer, suggestive of a loss of plasticity in macrophages adapted to other tissues.

Immunity 44, 755–768 (2016)