Contrastingly, enterotoxigenic Bacteroides fragilis (ETBF) is highly associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC), rapidly inducing IL-17-dependent murine colitis and tumorigenesis.
Importantly, intestinal NIK signaling is active in mouse models of colitis and patients with inflammatory bowel diseases; meanwhile, constitutive NIK signaling increases the susceptibility to inflammatory injury by inducing ectopic M-cell differentiation and a chronic increase of IL-17A.
Notably, lentivirus-mediated overexpression of Ascl2 remarkably alleviated the severity of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis in mice, with decreased level of colonic IL-17A.
In addition, key cytokines associated with colitis (IL-1β, IL-6, and IL-17A) were significantly suppressed, following treatment with M2b macrophage exosomes.
RhoA<sup>ΔCD4</sup> mice had a similar phenotype to Pggt1b<sup>ΔCD4</sup> mice, including development of colitis, increased numbers of CD4+ T cells in colon, increased expression of integrin alpha4beta7 by CD4+ T cells, and increased levels of IL17A and other inflammatory cytokines in lamina propria.
In a 2,4,6-trinitrobenzenesulfonic acid-induced colitis model, mice carrying VDR deletion in gut epithelial cells [VDRflox/flox (VDRf/f);Villin-Cre or VDRΔIEC] or in colonic epithelial cells (VDRf/f;CDX2-Cre or VDRΔCEC) developed more severe clinical colitis than VDRf/f control mice, characterized by more robust T-helper (TH)1 and TH17 responses, with greater increases in mucosal interferon (IFN)-γ+, interleukin (IL)-17+, and IFN-γ+IL-17+ T cells.
Suppression of IL-17F, but not of IL-17A, provides protection against colitis by inducing T<sub>reg</sub> cells through modification of the intestinal microbiota.
Notably, in vivo inhibition of miR-425 significantly alleviated the disease severity of TNBS-induced colitis in mice, with down-regulated levels of IL-17A.
Compared with the control group, TNBS‑treated mice had significantly higher secretion of IL‑17, higher DAI scores, a lower ratio of Treg, reduced colon lengths and higher histological scores for colon inflammation.
We blocked the IL-17A of the mouse model of TNBS-induced experimental intestinal colitis and fibrosis to further verify the potential inductive effect of IL-17A on EMT in vivo.
SCFAs mix protected from AOM/DSS-induced colorectal cancer by improving colon inflammation and disease activity index score as well as suppressing the expression of proinflammatory cytokines including IL-6, TNF-α and IL-17.
In the absence of IFNγ, intestinal inflammation in CD4 T cell recipient mice was associated with enhanced IL17 responses; consequently, targeting IL17 signaling in IFNγ-deficient mice reduced T cell-mediated colitis.
Consistent with this, IL-17-induced inflammation is significantly reduced in <i>NDR1-</i>deficient mice, and NDR1 deficiency significantly protects mice from MOG-induced experimental autoimmune encephalomyelitis (EAE) and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis likely by its inhibition of IL-17-mediated signaling pathway.
IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF.
Therefore, our results demonstrated that consumption of HSD <i>per se</i> triggered a histologically detectable inflammation in the colon and also exacerbated chemically induced models of colitis in mice by a mechanism dependent on IL-17 production most likely by both ILC3 and Th17 cells.