Publication Date:
2011-09-17
Description:
Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor-alpha production in spleen by a mechanism requiring acetylcholine signaling through the alpha7 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548937/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosas-Ballina, Mauricio -- Olofsson, Peder S -- Ochani, Mahendar -- Valdes-Ferrer, Sergio I -- Levine, Yaakov A -- Reardon, Colin -- Tusche, Michael W -- Pavlov, Valentin A -- Andersson, Ulf -- Chavan, Sangeeta -- Mak, Tak W -- Tracey, Kevin J -- R01 GM057226/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Oct 7;334(6052):98-101. doi: 10.1126/science.1209985. Epub 2011 Sep 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21921156" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylcholine/*biosynthesis
;
Action Potentials
;
Animals
;
CD4-Positive T-Lymphocytes/*immunology/*metabolism
;
Choline O-Acetyltransferase/metabolism
;
Cholinergic Agents/metabolism
;
Female
;
*Immunity, Innate
;
Immunologic Memory
;
Inflammation
;
Lymphocyte Activation
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Mice, Nude
;
*Neuroimmunomodulation
;
Norepinephrine/pharmacology
;
Receptors, Nicotinic/metabolism
;
Signal Transduction
;
Spleen/immunology/innervation/metabolism
;
T-Lymphocyte Subsets/immunology/metabolism
;
Tumor Necrosis Factor-alpha/blood
;
Vagus Nerve/*physiology
;
Vagus Nerve Stimulation
;
alpha7 Nicotinic Acetylcholine Receptor
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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