title: Vagotomy affects the development of oral tolerance and increases susceptibility to develop colitis independently of the alpha-7 nicotinic receptor.
abstract: Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR-/-mice. VGX, but not α7nAChR deficiency, prevented oral tolerance establishment. This effect was associated with reduced Treg conversion in thelamina propriaand mesenteric lymphnodes. To the same extent, vagotomized mice, but not α7nAChR-/-mice, developed a more severe DSS colitis compared with control mice treated with DSS, associated with a decreased number of colonic Tregs. However, neither VGX nor absence of α7nAChR in recipient mice affected colitis development in the T cell transfer model. In line, deficiency of α7nAChR exclusively in T cells did not influence the development of colitis induced by T cell transfer. Our results indicate a key role for the vagal intestinal innervation in the development of oral tolerance and colitis, most likely by modulating induction of Tregs independently of α7nAChR.
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center in Gastrointestinal Disorders (TARGID), Division of Gastroenterology, KU Leuven, Leuven, Belgium.
authors.forename: Martina
authors.initials: M
authors.lastname: Di Giovangiulio
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center in Gastrointestinal Disorders (TARGID), Division of Gastroenterology, KU Leuven, Leuven, Belgium.
authors.forename: Goele
authors.initials: G
authors.lastname: Bosmans
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center in Gastrointestinal Disorders (TARGID), Division of Gastroenterology, KU Leuven, Leuven, Belgium.
authors.forename: Elisa
authors.initials: E
authors.lastname: Meroni
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center in Gastrointestinal Disorders (TARGID), Division of Gastroenterology, KU Leuven, Leuven, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Stakenborg
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center in Gastrointestinal Disorders (TARGID), Division of Gastroenterology, KU Leuven, Leuven, Belgium.
authors.forename: Morgane
authors.initials: M
authors.lastname: Florens
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center in Gastrointestinal Disorders (TARGID), Division of Gastroenterology, KU Leuven, Leuven, Belgium.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Farro
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center in Gastrointestinal Disorders (TARGID), Division of Gastroenterology, KU Leuven, Leuven, Belgium.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Gomez-Pinilla
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center in Gastrointestinal Disorders (TARGID), Division of Gastroenterology, KU Leuven, Leuven, Belgium.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Matteoli
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center in Gastrointestinal Disorders (TARGID), Division of Gastroenterology, KU Leuven, Leuven, Belgium.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Boeckxstaens
keywords: T regulatory cells; Vagus nerve; colitis; oral tolerance; α7nAChR