Crosstalk between Muscularis Macrophages and Enteric Neurons Regulates Gastrointestinal Motility

• Muscularis macrophages produce BMP2 that activates BMPR on enteric neurons
• Enteric neurons produce CSF1 that promotes homeostasis of muscularis macrophages
• Macrophage-neuronal crosstalk regulates constitutive gastrointestinal motility
• Macrophage-neuronal crosstalk is driven by gut microbiota

SummaryIntestinal 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 To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (79209 K)

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