Microbiota and Gut Health: Promising Prospects for Clinical Trials from Bench to Bedside

Table 1

This table summarized the major IBD-related cytokines, showing their cellular source and explaining their IBD pathogenesis role.

Major cellular sources	Roles in IBD	References
CD4+ T cell, ILCs	(i) Increases permeability of intestinal vessels by disruption of VE-cadherin junctions, associated with increased inflammation and progression of IBD; (ii) IFNγ deficient mice show attenuated IBD symptoms	(i) Langer et al., [55]; (ii) Powrie et al. [35]
Th1 cell	(i) Increased TNF-alpha levels have been demonstrated in studies of patients with ulcerative colitis; (ii) Anti-TNF-alpha therapy is effective in ulcerative colitis; (iii) TNF binds to TNF receptor will activate c-Jun and NF-κB transcription factor. These two transcription factors involve in many inflammation encoded gene. As a result, induce inflammation at colon sites	(i) Pagnini and Cominelli, [56]; (ii) Schmitt, Neurath and Atreya, [57]
Th1 cell, intestine epithelial cells, Treg	(i) Inhibits both antigen presentation and subsequent proinflammatory cytokine release, resulting an unbalance between proinflammation and anti-inflammation cytokines	(i) Li and He, [40]
Th17 cell, ILCs	(i) IL17 signaling is able to induce a cascade of proinflammatory molecules like TNF, IFNγ, IL22, lymphotoxin, IL1β, and lipopolysaccharide (LPS). IL17A is known to mediate signaling synergistically to drive expression of inflammatory genes; (ii) Activated by IL-23 pathway as followed: when IL23 binds to its receptor, Jak2 and Tyk2 kinases are activated. This phosphorylates the receptor to create a docking site, which then causes STAT3 for the p19 subunit and STAT4 for the p40 subunit to be phosphorylated. The transcription of several effector cytokine genes in CD, including IL17A, is triggered by the activation of several pathways by the IL23R receptor	(i) Schmitt, Neurath and Atreya, [57]
Th17 cell	(i) IL-21 enhances NK cell activation and induces Th17 cell differentiation in IBD; (ii) The increased expression of IL21 gene was seen in UC patients	(i) Solaymani-Mohammadi et al., [58]
Regulatory T cells (Treg)	(i) Active TGF-β binds to its receptor and regulates mucosal immune reactions through the TGF-β signaling pathway. Dysregulated TGF-β signaling is observed in the intestines of IBD patients	(i) Ihara, Hirata and Koike, [59]