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J Pharmacol Sci. 2017 May;134(1):1-21. doi: 10.1016/j.jphs.2017.05.002. Epub 2017 May 12.

Physiological functions of the cholinergic system in immune cells.

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Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan.
Department of Anatomy, Division of Medicine, University of Fukui, Faculty of Medical Sciences, Matsuoka, Fukui 910-1193, Japan.
Department of Molecular Pharmacology, Kitasato University, School of Pharmaceutical Sciences, Minato-ku, Tokyo 108-8641, Japan. Electronic address:


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.


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

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