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

doi:10.1016/j.cell.2014.04.050

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.

Authors

Paul Andrew Muller¹, Balázs Koscsó², Gaurav Manohar Rajani², Korey Stevanovic³, Marie-Luise Berres⁴, Daigo Hashimoto⁴, Arthur Mortha⁴, Marylene Leboeuf⁴, Xiu-Min Li⁵, Daniel Mucida⁶, E Richard Stanley⁷, Stephanie Dahan⁸, Kara Gross Margolis³, Michael David Gershon⁹, Miriam Merad¹⁰, Milena Bogunovic¹¹

Affiliations

¹ Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; The Immunology Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
² Department of Microbiology and Immunology, Penn State University College of Medicine and Milton Hershey Medical Center, Hershey, PA 17033, USA.
³ Department of Pediatrics, Morgan Stanley Children's Hospital, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
⁴ Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; The Immunology Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA.
⁵ Division of Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA.
⁶ Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
⁷ Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
⁸ The Immunology Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA.
⁹ Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
¹⁰ Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; The Immunology Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA. Electronic address: miriam.merad@mssm.edu.
¹¹ Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; The Immunology Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY 10029, USA; Department of Microbiology and Immunology, Penn State University College of Medicine and Milton Hershey Medical Center, Hershey, PA 17033, USA. Electronic address: mbogunovich@hmc.psu.edu.

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:

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

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding