Starting from the observation that Tregs isolated from the lamina propria of active but not inactive IBD patients or uninflamed controls express Tbet and IFNγ, we investigated the functional role of Th1-like Tregs in the dextran sulfate model of colitis.
Mechanistically, our data showed that <i>F. nucleatum</i> aggravated dextran sodium sulfate (DSS)-induced colitis in the production of Th1-related cytokines IFN-γ through the AKT2 signaling pathway <i>in vitro</i> and <i>in vivo</i>.
Mice given NPD-0414-2 and NPD-0414-24 developed a significantly less severe form of TNBS colitis and exhibited reduced expression of IFN-γ and increased expression of IL-22.
We found that the incubation of MSCs with TNF-α and IFN-γ aggravates colitis, where high levels of pro-inflammatory factors, such as interleukin (IL)-17, IL-8, IL-12, IL-1β, transforming growth factor (TGF)-β, TNF-α and IFN-γ, were secreted.
Together, these findings indicate that GILZ controls IFN-γ production in B cells, which also affects T cell activity, and increased production of IFN-γ by B and T cells in LP is associated with predisposition to inflammatory colitis in mice.
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.
To investigate the functions of CD1d-dependent invariant natural killer T (iNKT) cells in experimental colitis induced in Yeti mice with dysregulated expression of IFNγ, we generated iNKT cell-deficient Yeti/CD1d KO mice and compared colitis among WT, CD1d KO, Yeti, and Yeti/CD1d KO mice following DSS treatment.
ITE also reversed the systemic and intestinal frequency of CD4<sup>+</sup> T cells during colitis and suppressed inflammatory cytokines including IFN-γ, TNF-α, IL-17, IL-6, and IL-1 as well as induced IL-10 levels.
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.
Colitis-derived inflammatory mediators including interferon-γ and reactive oxygen species strongly inhibited Sirt6 protein expression in young adult mouse colonocyte (YAMC) cells.
Using a model of experimental colitis, we observed that mice lacking NFAT5 in T cells exhibited exacerbated intestinal colitis and enhanced expression of IFNγ in draining lymph nodes and colon.
Exposure of Interleukin 10 (il10)-deficient mice to cigarette smoke accelerated development of colitis and increased expression of interferon gamma in the small intestine compared to wild-type mice exposed to smoke.
Guided by an unbiased metabolomics screen, we identified tryptophan (Trp) metabolism as a major modifying pathway in interferon-γ (IFNγ)-dominant murine colitis.
Here, we show that the NF-κB protein c-Rel regulates the inflammatory potential of colonic IFN-γ(+)Thy1(+) ILCs to induce anti-CD40-mediated colitis in rag1(-/-) mice.
Colonic tissue isolated from murine colitis revealed that levels of IL-10R1 and suppressor of cytokine signaling 3 were increased in the epithelium and coincided with increased tissue IFN-γ and IL-10 cytokines.
[Nature 2010;464:1371-1375] recently reported the accumulation of IL-23-responsive innate lymphoid cells in the colon, the former capable of producing IL-17 and interferon γ and mediating innate colitis in mice.
Interleukin (IL)-23, IL-17A, IL-17F, and interferon-gamma (IFN-γ) are important mediators of inflammatory colitis and are potential therapeutic targets in inflammatory bowel disease (IBD).
Absolute numbers of IL-17(+) or IFN-γ(+) CD4(+) T cells per colon were less in mice receiving Daikenchuto than in mice that received control feed, as both groups received naive CD4(+) T cells to induce colitis.
APP administration dampened the mRNA expression of IL-1β, TNF-α, IL-6, IL-17, IL-22, CXCL9, CXCL10, CXCL11, and IFN-γ in the colons of mice with colitis.
Treatment of C3H.IL-10(-/-) mice with fenofibrate delayed the onset of colitis, decreased the colonic histopathology score, and decreased colonic expression of genes encoding the inflammatory cytokines interferon-gamma and interleukin (IL)-17.