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Science 334 (6052): 98-101

Copyright © 2011 by the American Association for the Advancement of Science

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

Mauricio Rosas-Ballina,1,* Peder S. Olofsson,1,* Mahendar Ochani,1 Sergio I. Valdés-Ferrer,1,2 Yaakov A. Levine,1 Colin Reardon,3 Michael W. Tusche,3 Valentin A. Pavlov,1 Ulf Andersson,4 Sangeeta Chavan,1 Tak W. Mak,3 Kevin J. Tracey1,{dagger}

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.

1 Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA.
2 Elmezzi Graduate School of Molecular Medicine, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA.
3 The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario M5G 2C1, Canada.
4 Department of Women’s and Children’s Health, Karolinska Institutet, S-171 76 Stockholm, Sweden.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: kjtracey{at}

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