title: Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility.
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:
authors.affiliation: 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.
authors.forename: Paul Andrew
authors.initials: PA
authors.lastname: Muller
authors.affiliation: Department of Microbiology and Immunology, Penn State University College of Medicine and Milton Hershey Medical Center, Hershey, PA 17033, USA.
authors.forename: Balázs
authors.initials: B
authors.lastname: Koscsó
authors.affiliation: Department of Microbiology and Immunology, Penn State University College of Medicine and Milton Hershey Medical Center, Hershey, PA 17033, USA.
authors.forename: Gaurav Manohar
authors.initials: GM
authors.lastname: Rajani
authors.affiliation: Department of Pediatrics, Morgan Stanley Children's Hospital, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Korey
authors.initials: K
authors.lastname: Stevanovic
authors.affiliation: 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.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Berres
authors.affiliation: 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.
authors.forename: Daigo
authors.initials: D
authors.lastname: Hashimoto
authors.affiliation: 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.
authors.forename: Arthur
authors.initials: A
authors.lastname: Mortha
authors.affiliation: 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.
authors.forename: Marylene
authors.initials: M
authors.lastname: Leboeuf
authors.affiliation: 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.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mucida
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
authors.affiliation: 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.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dahan
authors.affiliation: Department of Pediatrics, Morgan Stanley Children's Hospital, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Kara Gross
authors.initials: KG
authors.lastname: Margolis
authors.affiliation: Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Michael David
authors.initials: MD
authors.lastname: Gershon
authors.affiliation: 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.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: 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.
authors.forename: Milena
authors.initials: M
authors.lastname: Bogunovic
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D005769:Gastrointestinal Motility; D041981:Gastrointestinal Tract / Q000166:cytology* / Q000294:innervation / Q000382:microbiology* / Q000502:physiology; D066298:In Vitro Techniques; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010528:Peristalsis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D052006:Bone Morphogenetic Protein Receptors, Type II