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Review
. 2021 Dec 11:19:100401.
doi: 10.1016/j.bbih.2021.100401. eCollection 2022 Feb.

Cholinergic immunomodulation in inflammatory bowel diseases

Michele A Serafini  1   2 , Ana H Paz  3   2 , Natalia S Nunes  4
Affiliations
Review

Cholinergic immunomodulation in inflammatory bowel diseases

Michele A Serafini et al. Brain Behav Immun Health. .

Abstract

Inflammatory bowel diseases (IBD) are chronic intestinal disorders characterized by dysregulated immune responses to resident microbiota in genetically susceptible hosts. The activation of the cholinergic system has been proposed for the treatment of IBD patients according to its potential anti-inflammatory effect in vivo. The α-7-nicotinic-acetylcholine receptor (α7nAChR) is involved in the inhibition of inflammatory processes, modulating the production of cytokines, suppressing dendritic cells and macrophage activity, leading to the suppression of T cells. In this review, we address the most recent studies and clinical trials concerning cholinergic signaling and its therapeutic potential for inflammatory bowel diseases.

Keywords: Acetylcholine; Cholinergic signaling; Immunomodulation; Inflammatory bowel diseases; Intestinal immunity; Macrophage; T cell; Vagus nerve; α-7-Nicotinic-acetylcholine receptor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Vagus nerve stimulation and sacral nerve stimulation suppress inflammation in the spleen and in the colon via the cholinergic anti-inflammatory pathway. (a) Splenic and intestinal innervation by splenic nerve, vagus nerve and sacral nerve. (b) In the spleen, norepinephrine released by sympathetic splenic nerves binds to β2 adrenergic receptors on choline acetyltransferase (ChAT)+ CD4+ T-cells, which then synthetize and release acetylcholine (Ach). Thereafter, ACh binds to α7nAChR in splenic macrophages, inhibiting its activation and TNFα production. (c) In the large intestine, SNS and VNS activate myenteric neurons, which release ACh. In turn, ACh binds to α7nAChR in muscularis macrophages, inhibiting its activation and TNFα and interleukin (IL)-6 production. ∗The mechanisms of SNS circuit are still not clear; however, it has been observed that SNS does increase ACh tissue levels in the colon (Pasricha et al., 2020; Tu et al., 2020a). Figure Abbreviations: α7nAChR: α7-nicotinic-acetylcholine-receptor. ACh: acetylcholine. MMØ: muscularis macrophage. NE: norepinephrine. SNS: sacral nerve stimulation. TNFα: Tumor necrosis factor α. VNS: vagal nerve stimulation.
See this image and copyright information in PMC

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