Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis

Sebastiaan De Schepper, Simon Verheijden, Javier Aguilera-Lizarraga, Maria Francesca Viola, Werend Boesmans, Nathalie Stakenborg, Iryna Voytyuk, Inga Schmidt, Bram Boeckx, Isabelle Dierckx de Casterlé, Veerle Baekelandt, Erika Gonzalez Dominguez, Matthias Mack, Inge Depoortere, Bart De Strooper, Ben Sprangers, Uwe Himmelreich, Stefaan Soenen, Martin Guilliams, Pieter Vanden BergheElizabeth Jones, Diether Lambrechts, Guy Boeckxstaens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

262 Citations (Web of Science)


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.

Original languageEnglish
Pages (from-to)400-415.e13
Issue number2
Publication statusPublished - 4 Oct 2018
Externally publishedYes


  • Animals
  • Body Patterning/physiology
  • Cell Differentiation/genetics
  • Gastrointestinal Motility/immunology
  • Homeostasis
  • Inflammation/immunology
  • Intestinal Mucosa/immunology
  • Intestine, Small/metabolism
  • Intestines/immunology
  • Macrophages/immunology
  • Mice
  • Monocytes/metabolism
  • Neurons/metabolism
  • Phagocytes/immunology
  • Transcriptome
  • Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis

    De Schepper, S., Verheijden, S., Aguilera-Lizarraga, J., Viola, M. F., Boesmans, W., Stakenborg, N., Voytyuk, I., Schmidt, I., Boeckx, B., de Casterle, I. D., Baekelandt, V., Dominguez, E. G., Mack, M., Depoortere, I., De Strooper, B., Sprangers, B., Himmelreich, U., Soenen, S., Guilliams, M., Vanden Berghe, P., & 3 othersJones, E., Lambrechts, D. & Boeckxstaens, G., 24 Jan 2019, In: Cell. 176, 3, p. 676-676 1 p.

    Research output: Contribution to journalErratum / corrigendum / retractionsAcademic

    Open Access
    27 Citations (Web of Science)

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