Critical roles of acetylcholine and the muscarinic and nicotinic acetylcholine receptors in the regulation of immune function

Koichiro Kawashima, Takeshi Fujii, Yasuhiro Moriwaki, Hidemi Misawa

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Lymphocytes express both muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs, respectively), and stimulation of mAChRs and nAChRs produces various biochemical and functional changes. Although it has been postulated that parasympathetic cholinergic nerves directly innervate immune cells, no evidence has supported this hypothesis. We measured ACh in the blood of various animal species and determined its localization in T cells using a sensitive and specific radioimmunoassay. Furthermore, we showed that T cells express choline acetyltransferase (ChAT), an ACh synthesizing enzyme. Immunological T cell activation enhances ACh synthesis through the up-regulation of ChAT expression, suggesting lymphocytic cholinergic activity is related to immunological activity. Most immune cells such as T cells, B cells, and monocytes express all five subtypes of mAChRs (M1-M5), and various subunits of the nAChR, such as α3, α5, α7, α9, and α10. Studies on serum antibody production in M1 and M 5 combined mAChR gene knockout (KO) mice immunized with ovalbumin (OVA) revealed that M1/M5 mAChRs up-regulate TNF-α, IFN-γ and IL-6 production in spleen cells, leading to an elevation of serum anti-OVA specific IgG1. In contrast, studies of nAChR α7 subunit gene KO mice immunized with OVA show that α7 nAChRs down-regulate these proinflammatory cytokines, thereby leading to a reduction of anti-OVA specific IgG1. Taken together, these findings demonstrate that both mAChRs and nAChRs modulate production of cytokines, such as TNF-α, resulting in a modification of antibody production. These findings support the notion that a non-neuronal cholinergic system is involved in the regulation of immune cell function.

Original languageEnglish
Pages (from-to)1027-1032
Number of pages6
JournalLife Sciences
Volume91
Issue number21-22
DOIs
Publication statusPublished - 2012 Nov 27

Fingerprint

T-cells
Ovalbumin
Nicotinic Receptors
Muscarinic Receptors
Acetylcholine
Cholinergic Agents
T-Lymphocytes
Gene Knockout Techniques
Choline O-Acetyltransferase
Knockout Mice
Antibody Formation
Up-Regulation
Immunoglobulin G
Genes
Cytokines
Lymphocytes
Antibodies
Serum
Radioimmunoassay
Monocytes

Keywords

  • B cell
  • Choline acetyltransferase
  • Cytokine
  • IgG
  • IL-6
  • T cell

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Critical roles of acetylcholine and the muscarinic and nicotinic acetylcholine receptors in the regulation of immune function. / Kawashima, Koichiro; Fujii, Takeshi; Moriwaki, Yasuhiro; Misawa, Hidemi.

In: Life Sciences, Vol. 91, No. 21-22, 27.11.2012, p. 1027-1032.

Research output: Contribution to journalArticle

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