TY - JOUR
T1 - Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility
AU - Muller, Paul Andrew
AU - Koscsó, Balázs
AU - Rajani, Gaurav Manohar
AU - Stevanovic, Korey
AU - Berres, Marie Luise
AU - Hashimoto, Daigo
AU - Mortha, Arthur
AU - Leboeuf, Marylene
AU - Li, Xiu Min
AU - Mucida, Daniel
AU - Stanley, E. Richard
AU - Dahan, Stephanie
AU - Margolis, Kara Gross
AU - Gershon, Michael David
AU - Merad, Miriam
AU - Bogunovic, Milena
N1 - Funding Information:
We thank members of the Immgen Project ( http://www.immgen.org ) for performing a whole-mouse genome microarray and the Penn State Hershey Flow Cytometry Core Facility and the Mount Sinai Flow Cytometry Core for assistance with our experiments. We also thank Frederico Costa Pinta (Rockefeller University, New York, NY, and School of Veterinary Medicine, University of Sao Paulo, Brazil), Hongyan Zou (Icahn School of Medicine at Mount Sinai Hospital, New York, NY), and Florent Ginhoux (Singapore Immunology Network and Agency for Science, Technology and Research, Singapore) for productive discussions regarding the study, and Aron Lukacher (Penn State University College of Medicine, Hershey, PA) for help with the manuscript. This work was supported in part by grants from the NIH (AI09561, CA173861, and AI104848 to M.M.; CA32551 to E.R.S; and R21-AI105047 to D.M.), as well as a Career Development Award from the CCFA and PCARS from the NIAID (M.B.).
PY - 2014/7/17
Y1 - 2014/7/17
N2 - 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
AB - 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
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U2 - 10.1016/j.cell.2014.04.050
DO - 10.1016/j.cell.2014.04.050
M3 - Article
C2 - 25036630
AN - SCOPUS:84904573974
SN - 0092-8674
VL - 158
SP - 300
EP - 313
JO - Cell
JF - Cell
IS - 2
ER -