Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit
Mauricio Rosas-Ballina, Peder S Olofsson, Mahendar Ochani, Sergio I Valdés-Ferrer, Yaakov A Levine, Colin Reardon, Michael W Tusche, Valentin A Pavlov, Ulf Andersson, Sangeeta Chavan, Tak W Mak, Kevin J Tracey, Mauricio Rosas-Ballina, Peder S Olofsson, Mahendar Ochani, Sergio I Valdés-Ferrer, Yaakov A Levine, Colin Reardon, Michael W Tusche, Valentin A Pavlov, Ulf Andersson, Sangeeta Chavan, Tak W Mak, Kevin J Tracey
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.
Figures
Source: PubMed