Colitis-derived inflammatory mediators including interferon-γ and reactive oxygen species strongly inhibited Sirt6 protein expression in young adult mouse colonocyte (YAMC) cells.
[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).
We then demonstrated that NOD2-deficient mice adoptively transferred OVA-specific CD4+ T cells and that administered intrarectal ECOVA developed colitis associated with the expansion of OVA-specific CD4+ T cells producing IFN-gamma.
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.
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.
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>.
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.
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.
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.
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.
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.
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.
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.
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.
Guided by an unbiased metabolomics screen, we identified tryptophan (Trp) metabolism as a major modifying pathway in interferon-γ (IFNγ)-dominant murine 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.
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.
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.