Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit |
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| Authors: | Rosas-Ballina Mauricio Olofsson Peder S Ochani Mahendar Valdés-Ferrer Sergio I Levine Yaakov A Reardon Colin Tusche Michael W Pavlov Valentin A Andersson Ulf Chavan Sangeeta Mak Tak W Tracey Kevin J |
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| Institution: | Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA. |
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| 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. |
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