title: Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.
abstract: Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor-α production in spleen by a mechanism requiring acetylcholine signaling through the α7 nicotinic acetylcholine receptor expressed on cytokine-producing macrophages. Nerve fibers in spleen lack the enzymatic machinery necessary for acetylcholine production; therefore, how does this neural circuit terminate in cholinergic signaling? We identified an acetylcholine-producing, memory phenotype T cell population in mice that is integral to the inflammatory reflex. These acetylcholine-producing T cells are required for inhibition of cytokine production by vagus nerve stimulation. Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitter, acetylcholine, required to control innate immune responses.
authors.affiliation: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rosas-Ballina
authors.forename: Peder S
authors.initials: PS
authors.lastname: Olofsson
authors.forename: Mahendar
authors.initials: M
authors.lastname: Ochani
authors.forename: Sergio I
authors.initials: SI
authors.lastname: Valdés-Ferrer
authors.forename: Yaakov A
authors.initials: YA
authors.lastname: Levine
authors.forename: Colin
authors.initials: C
authors.lastname: Reardon
authors.forename: Michael W
authors.initials: MW
authors.lastname: Tusche
authors.forename: Valentin A
authors.initials: VA
authors.lastname: Pavlov
authors.forename: Ulf
authors.initials: U
authors.lastname: Andersson
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Chavan
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis*; D000200:Action Potentials; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D007156:Immunologic Memory; D007249:Inflammation; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015213:Neuroimmunomodulation; D009638:Norepinephrine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000294:innervation / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014630:Vagus Nerve / Q000502:physiology*; D055536:Vagus Nerve Stimulation; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D018678:Cholinergic Agents; C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D009638:Norepinephrine