Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility

Paul Andrew Muller, Balázs Koscsó, Gaurav Manohar Rajani, Korey Stevanovic, Marie Luise Berres, Daigo Hashimoto, Arthur Mortha, Marylene Leboeuf, Xiu Min Li, Daniel Mucida, E. Richard Stanley, Stephanie Dahan, Kara Gross Margolis, Michael David Gershon, Miriam Merad, Milena Bogunovic

Research output: Contribution to journalArticle

225 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)300-313
Number of pages14
JournalCell
Volume158
Issue number2
DOIs
StatePublished - Jul 17 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Muller, P. A., Koscsó, B., Rajani, G. M., Stevanovic, K., Berres, M. L., Hashimoto, D., Mortha, A., Leboeuf, M., Li, X. M., Mucida, D., Stanley, E. R., Dahan, S., Margolis, K. G., Gershon, M. D., Merad, M., & Bogunovic, M. (2014). Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell, 158(2), 300-313. https://doi.org/10.1016/j.cell.2014.04.050