期刊
CELL
卷 175, 期 2, 页码 400-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2018.07.048
关键词
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资金
- European Research Council (ERC) Advanced Grant (ERC-2013-Adg) [340101]
- Research Foundation Flanders [12J8117N]
- KU Leuven [C12/16/019]
- ERA-NET
- [AKUL 15/37]
- MRC [UKDRI-1004] Funding Source: UKRI
- European Research Council (ERC) [340101] Funding Source: European Research Council (ERC)
Macrophages are highly heterogeneous tissue-resident immune cells that perform a variety of tissue- supportive functions. The current paradigm dictates that intestinal macrophages are continuously replaced by incoming monocytes that acquire a pro-inflammatory or tissue-protective signature. Here, we identify a self-maintaining population of macrophages that arise from both embryonic precursors and adult bone marrow-derived monocytes and persists throughout adulthood. Gene expression and imaging studies of self-maintaining macrophages revealed distinct transcriptional profiles that reflect their unique localization (i.e., closely positioned to blood vessels, submucosal and myenteric plexus, Paneth cells, and Peyer's patches). Depletion of self-maintaining macrophages resulted in morphological abnormalities in the submucosal vasculature and loss of enteric neurons, leading to vascular leakage, impaired secretion, and reduced intestinal motility. These results provide critical insights in intestinal macrophage heterogeneity and demonstrate the strategic role of self-maintaining macrophages in gut homeostasis and intestinal physiology.
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