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Review
. 2020 Feb 20:11:180.
doi: 10.3389/fimmu.2020.00180. eCollection 2020.

Transient Receptor Potential Channels and Inflammatory Bowel Disease

Yiding Chen  1   2 , Jingxi Mu  1   2 , Min Zhu  1   2 , Arjudeb Mukherjee  3 , Hu Zhang  1   2
Affiliations
Review

Transient Receptor Potential Channels and Inflammatory Bowel Disease

Yiding Chen et al. Front Immunol. .

Abstract

The transient receptor potential (TRP) cation channels are present in abundance across the gastrointestinal (GI) tract, serving as detectors for a variety of stimuli and secondary transducers for G-protein coupled receptors. The activation of TRP channels triggers neurogenic inflammation with related neuropeptides and initiates immune reactions by extra-neuronally regulating immune cells, contributing to the GI homeostasis. However, under pathological conditions, such as inflammatory bowel disease (IBD), TRP channels are involved in intestinal inflammation. An increasing number of human and animal studies have indicated that TRP channels are correlated to the visceral hypersensitivity (VHS) and immune pathogenesis in IBD, leading to an exacerbation or amelioration of the VHS or intestinal inflammation. Thus, TRP channels are a promising target for novel therapeutic methods for IBD. In this review, we comprehensively summarize the functions of TRP channels, especially their potential roles in immunity and IBD. Additionally, we discuss the contradictory findings of prior studies and offer new insights with regard to future research.

Keywords: gastrointestinal tract; immune cells; inflammatory bowel disease; neurogenic inflammation; transient receptor potential channels.

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Figures

Figure 1
Figure 1
The overview of TRP channels involved in IBD. The TRP channels mainly express themselves on extrinsic primary afferents in the intestine. TRP channels directly detect various stimuli in the intestinal lumen and act as secondary transducers for GPCR. Specially, TRPV1 and TRPA1 can crosstalk with microbiota through TLR4 or in a TLR4-independent manner. Upon activation, TRP channels transduce the sensory signal to the central nervous system and lead to autonomic reflex responses. This mechanism could be enhanced by inflammatory mediators and be responsible for the visceral hypersensitivity on pathological conditions. Meanwhile, the activation of TRP channels triggers neurogenic inflammation with neuropeptides, such as CGRP and SP, which can interact with immune cells. On the other hand, TRP channels express on multiple immune cells and regulate their functions, thus promoting or restraining the initiation or process of inflammation. Therefore, based on the immunomodulatory effects, TRP channels play a role in the immune pathogenesis of IBD. GPCR, G-protein coupled receptors; TLR4, Toll-like receptor 4; SP, substance P; CGRP, calcitonin-gene-related peptide; TNF-α, tumor necrosis factor alpha; IFN-γ, interferon gamma; MCP-1, macrophage chemoattractant protein-1; MPO, myeloperoxidase; ROS, reactive oxygen species.
Figure 2
Figure 2
The stimulation of TRP channels and the downstream regulatory network in IBD. TRP channels, together with other primary factors, play a role in the pathogenesis of IBD. The stimulation of TRP channels is based on the exogenous stimuli and the endogenous stimuli. The latter mainly refer to the mediators synthesized and released within the progress of colitis. The activated TRP channels can induce the release of neuropeptides and cytokines, thus leading to the pro- or anti-inflammatory effects. In addition to neurons and immune cells, there are other TRP channels-expressing cells and cellular pathways contributing to regulate the intestinal inflammation, while the definite functions of these cells and pathways are unclear. The complicated crosstalk amongst the neuropeptides, cytokines, TRP channels-expressing cells, and diverse cellular pathways results in the various but elusive effects induced by the stimulation of TRP channels in IBD.
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