title: Central cholinergic activation of a vagus nerve-to-spleen circuit alleviates experimental colitis.
abstract: The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and α7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility complex II level and pro-inflammatory cytokine secretion by splenic CD11c⁺ cells mediated by α7nAChR signaling. The cholinergic anti-inflammatory efficacy was abolished in mice with vagotomy, splenic neurectomy, or splenectomy. In conclusion, central cholinergic activation of a vagus nerve-to-spleen circuit controls intestinal inflammation and this regulation can be explored to develop novel therapeutic strategies.
authors.affiliation: Department of Immunology and Internal Medicine Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Immunology and Internal Medicine Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: M F
authors.initials: MF
authors.lastname: Rabbi
authors.affiliation: Department of Immunology and Internal Medicine Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Labis
authors.affiliation: Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Pavlov
authors.affiliation: Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Tracey
authors.affiliation: 1] Department of Immunology and Internal Medicine Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada [2] Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J E
authors.initials: JE
authors.lastname: Ghia
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005702:Galantamine / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D011976:Receptors, Muscarinic / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000294:innervation / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D002800:Cholinesterase Inhibitors; D016207:Cytokines; D008024:Ligands; D011976:Receptors, Muscarinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005702:Galantamine