Abstract
J Exp Med. 2026 May 4;223(5):e20240801. doi: 10.1084/jem.20240801. Epub 2026 Apr 21.
ABSTRACT
Macrophages localize in sub-tissular niches associated with their ontogeny and activity. In the intestine, a paradigm has emerged that long-lived macrophages are present in the muscular layer, while highly monocyte-replenished populations are found in the lamina propria (LP). Whether long-lived macrophages are restricted in such a simplified manner has not been well explored. Moreover, the impact of specific gut-associated factors on macrophage identity across intestinal tissue layers is unknown. We generated scRNA-seq data from WT and Ccr2-/- mice to identify phenotypic features of long-lived macrophage populations in distinct intestinal layers and identified CD163 as a marker to distinguish submucosal/muscularis (S/M) from LP macrophages. Challenging the emerging paradigm, long-lived macrophages were found in the LP and S/M, with distinct transcriptomes and responsiveness to proinflammatory stimuli. Employing transgenic mice, we demonstrate a critical role for TGF-β signalling in maintaining the identity of long-lived LP but not S/M macrophages and that macrophage-derived TGF-β1 is required to instruct intestinal macrophage identity after development.
PMID:42012484 | DOI:10.1084/jem.20240801
UK DRI Authors
