V Jayaraman, Ian Prise, Verena Kästele, Sabrina; id_orcid 0000-0003-3454-149X Tamburrano, Kelly Wemyss, Hayley Bridgeman, Rufus; id_orcid 0000-0003-1258-937X Daw, Patrick Strangward, Alfie Sanderson, Sheena Cruickshank, Joanne E. Konkel, Christine Chew, Chengcan Yao, CJ Anderson, Josef Priller, Barry McColl, David A. D. Munro, Liesbet Martens, Charlotte L. Scott, Martin Guilliams, Antony; id_orcid 0000-0002-5408-0013 Adamson, John; id_orcid 0000-0002-4052-5923 Grainger, Tovah N. Shaw
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.