Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility

Cell. 2014 Jul 17;158(2):300-313. doi: 10.1016/j.cell.2014.04.050.


Intestinal peristalsis is a dynamic physiologic process influenced by dietary and microbial changes. It is tightly regulated by complex cellular interactions; however, our understanding of these controls is incomplete. A distinct population of macrophages is distributed in the intestinal muscularis externa. We demonstrate that, in the steady state, muscularis macrophages regulate peristaltic activity of the colon. They change the pattern of smooth muscle contractions by secreting bone morphogenetic protein 2 (BMP2), which activates BMP receptor (BMPR) expressed by enteric neurons. Enteric neurons, in turn, secrete colony stimulatory factor 1 (CSF1), a growth factor required for macrophage development. Finally, stimuli from microbial commensals regulate BMP2 expression by macrophages and CSF1 expression by enteric neurons. Our findings identify a plastic, microbiota-driven crosstalk between muscularis macrophages and enteric neurons that controls gastrointestinal motility. PAPERFLICK:

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Morphogenetic Protein Receptors, Type II / metabolism
  • Gastrointestinal Motility*
  • Gastrointestinal Tract / cytology*
  • Gastrointestinal Tract / innervation
  • Gastrointestinal Tract / microbiology*
  • Gastrointestinal Tract / physiology
  • In Vitro Techniques
  • Macrophage Colony-Stimulating Factor
  • Macrophages / metabolism*
  • Mice
  • Neurons / metabolism
  • Peristalsis
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism
  • Signal Transduction


  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Macrophage Colony-Stimulating Factor
  • Receptor, Macrophage Colony-Stimulating Factor
  • Bone Morphogenetic Protein Receptors, Type II