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Tissue-resident macrophages in the intestine are long-lived and defined by Tim-4 and CD4 expression

ABSTRACT: A defining feature of resident gut macrophages is their high replenishment rate from blood monocytes, attributed to tonic commensal-stimulation of this site. In contrast, almost all other tissues contain locally maintained macrophage populations, which co-exist with monocyte-replenished cells at homeostasis. Here, we identified three transcriptionally distinct murine gut macrophage subsets that segregate based on expression of Tim-4 and CD4. Challenging current understanding, Tim-4+CD4+ gut macrophages were found to be locally maintained, while Tim-4–CD4+ macrophages had a slow turnover from blood monocytes; indeed, Tim-4–CD4– macrophages were the only subset with the high monocyte-replenishment rate currently attributed to gut macrophages. Moreover, all macrophage subpopulations required a live microbiota to sustain their numbers, not only those derived from blood monocytes. These findings oppose the prevailing paradigm that all macrophages in the adult murine gut rapidly turnover from monocytes in a microbiome-dependant manner; instead, supplanting it with a model of ontogenetic diversity, where locally maintained subsets co-exist with rapidly replaced, monocyte-derived populations.

ORGANISM(S): Mus musculus

PROVIDER: GSE114434 | GEO | 2018/05/15

REPOSITORIES: GEO

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