Physiological functions of the cholinergic system in immune cells

Takeshi Fujii, Masato Mashimo, Yasuhiro Moriwaki, Hidemi Misawa, Shiro Ono, Kazuhide Horiguchi, Koichiro Kawashima

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

T and B cells, macrophages and dendritic cells (DCs) all express most of the components necessary for a functional cholinergic system. This includes choline acetyltransferase (ChAT), muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs, respectively) and acetylcholinesterase (AChE). Immunological activation of T cells up-regulates cholinergic activity, including ChAT and AChE expression. Moreover, toll-like receptor agonists induce ChAT expression in DCs and macrophages, suggesting cholinergic involvement in the regulation of immune function. Immune cells express all five M1–M5 mAChR subtypes and several nAChR subtypes, including α7. Modulation of antigen-specific antibody and pro-inflammatory cytokine production in M1/M5 mAChR gene-knockout (KO) and α7 nAChR-KO mice further support the idea of a non-neuronal cholinergic system contributing to the regulation of immune function. Evidence also suggests that α7 nAChRs are involved in suppressing DC and macrophage activity, leading to suppression of T cell differentiation into effector T cells. These findings suggest the possibility that immune function could be modulated by manipulating immune cell cholinergic activity using specific agonists and antagonists. Therefore, a fuller understanding of the immune cell cholinergic system should be useful for the development of drugs and therapeutic strategies for the treatment of inflammation-related diseases and cancers.

Original languageEnglish
Pages (from-to)1-21
Number of pages21
JournalJournal of Pharmacological Sciences
Volume134
Issue number1
DOIs
Publication statusPublished - 2017 May 1

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Cholinergic Agents
Immune System
Choline O-Acetyltransferase
Dendritic Cells
T-Lymphocytes
Macrophages
Acetylcholinesterase
Gene Knockout Techniques
Toll-Like Receptors
Nicotinic Receptors
Muscarinic Receptors
Knockout Mice
Cell Differentiation
B-Lymphocytes
Up-Regulation
Cytokines
Inflammation
Antigens
Antibodies
Pharmaceutical Preparations

Keywords

  • Acetylcholine receptor
  • Choline acetyltransferase
  • Dendritic cell
  • Lymphocyte
  • Macrophage

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Physiological functions of the cholinergic system in immune cells. / Fujii, Takeshi; Mashimo, Masato; Moriwaki, Yasuhiro; Misawa, Hidemi; Ono, Shiro; Horiguchi, Kazuhide; Kawashima, Koichiro.

In: Journal of Pharmacological Sciences, Vol. 134, No. 1, 01.05.2017, p. 1-21.

Research output: Contribution to journalReview article

Fujii, Takeshi ; Mashimo, Masato ; Moriwaki, Yasuhiro ; Misawa, Hidemi ; Ono, Shiro ; Horiguchi, Kazuhide ; Kawashima, Koichiro. / Physiological functions of the cholinergic system in immune cells. In: Journal of Pharmacological Sciences. 2017 ; Vol. 134, No. 1. pp. 1-21.
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AB - T and B cells, macrophages and dendritic cells (DCs) all express most of the components necessary for a functional cholinergic system. This includes choline acetyltransferase (ChAT), muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs, respectively) and acetylcholinesterase (AChE). Immunological activation of T cells up-regulates cholinergic activity, including ChAT and AChE expression. Moreover, toll-like receptor agonists induce ChAT expression in DCs and macrophages, suggesting cholinergic involvement in the regulation of immune function. Immune cells express all five M1–M5 mAChR subtypes and several nAChR subtypes, including α7. Modulation of antigen-specific antibody and pro-inflammatory cytokine production in M1/M5 mAChR gene-knockout (KO) and α7 nAChR-KO mice further support the idea of a non-neuronal cholinergic system contributing to the regulation of immune function. Evidence also suggests that α7 nAChRs are involved in suppressing DC and macrophage activity, leading to suppression of T cell differentiation into effector T cells. These findings suggest the possibility that immune function could be modulated by manipulating immune cell cholinergic activity using specific agonists and antagonists. Therefore, a fuller understanding of the immune cell cholinergic system should be useful for the development of drugs and therapeutic strategies for the treatment of inflammation-related diseases and cancers.

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