Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis.
De Schepper Sebastiaan,Verheijden Simon,Aguilera-Lizarraga Javier,Viola Maria Francesca,Boesmans Werend,Stakenborg Nathalie,Voytyuk Iryna,Schmidt Inga,Boeckx Bram,Dierckx de Casterlé Isabelle,Baekelandt Veerle,Gonzalez Dominguez Erika,Mack Matthias,Depoortere Inge,De Strooper Bart,Sprangers Ben,Himmelreich Uwe,Soenen Stefaan,Guilliams Martin,Vanden Berghe Pieter,Jones Elizabeth,Lambrechts Diether,Boeckxstaens Guy
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.