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Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit

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Science  15 Sep 2011:
1209985
DOI: 10.1126/science.1209985

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 alpha 7 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 were required for the 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.