Unexpectedly, IL-12, IL-1β and CD163-, but not CD163+, cells induced IL-8 expression in colonic CD4+T cells, which co-expressed IFN-γ and/or IL-17 in UC and not CD.
Experimental evidence "proves" that IL-17 plays a critical role in the pathogenesis of inflammatory bowel disease, but blocking IL-17 makes Crohn's disease worse.
To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease.
Serum JKAP level in CD patients was lower compared to HCs, and it disclosed a good predictive value for decreased CD risk; meanwhile, it was negatively correlated with CRP level, CDAI score, TNF-α, interleukin (IL)-6, and IL-17 levels in CD patients.
It is suggested that IL-23/IL-17 axis and single nucleotide polymorphisms (SNPs) of <i>IL23R</i> may have crucial role in pathogenesis of Crohn's disease (CD).
This is the first case report of de-novo severe Crohn's-like IBD in association with the use of Ixekizumab requiring rescue with escalated dosing of anti-TNF therapy and highlights the importance of close monitoring in patients being treated with IL-17 inhibitors, especially in those patients with known risk factors for inflammatory bowel disease.
IL-23-mediated Th-17 cell activation and stimulation of IL-17-driven pro-inflammatory axis has been associated with autoimmunity disorders such as Inflammatory Bowel Disease (IBD) or Crohn’s Disease (CD).
One of the diseases that has benefitted most from this technology has been Crohn's disease (CD), with the identification of autophagy, the IL-17/IL-23 axis and innate lymphoid cells as key players in CD pathogenesis.
Serum concentrations of IL-17A (64.2 ± 17.2 vs. 28.3 ± 10.0) and IL-22 (37.5 ± 8.8 vs. 27.2 ± 3.7) were significantly higher in ulcerative colitis than those in Crohn's disease.
In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P = .001; area under the receiver operating characteristic curve, 0.72).
Serum TNF-α and IL-17A levels were increased in active CD or UC patients, and positively correlated with CD99 expression in PBMCs (CD: r = .402, p = .009; r = .350, p = .025.
Plasma miR-125a expression was decreased in A-CD patients compared with that in R-CD patients (<i>P</i> < 0.001) and HCs (<i>P</i> < 0.001). miR-125a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve (AUC) = 0.854] and from HCs (AUC = 0.780), whereas miR-125b expression did not. miR-125a was negatively correlated with C-reaction protein (CRP) (<i>P</i> = 0.017), erythrocyte sedimentation rate (ESR) (<i>P</i> = 0.026), Crohn's disease activity index (CDAI) (<i>P</i> = 0.003), IL-17 (<i>P</i> = 0.015), and TNF-α (<i>P</i> = 0.004) in A-CD patients.
We found that the frequency of IFN-γ- and IL-17-expressing CD4 T cells was significantly higher after stimulation with CD bacteria than with non-CD bacteria, while the frequency of IL-4- and IL-10-expressing CD4 T cells was significantly decreased after stimulation with CD bacteria.
Elevated levels of IL-4 (2.91-fold) and IL-13 (4.05-fold) mRNA were detected in the inflamed colon mucosa of patients with ulcerative colitis (UC), IFN-γ mRNA was upregulated (3.23-fold) in the inflamed colon mucosa of patients with Crohn's disease (CD), whereas upregulation of IL-17A and TL1A mRNA was present in the inflamed colon mucosa of patients with both CD and UC (IL-17A: 4.48-fold and 2.74-fold, TL1A: 3.19-fold and 3.22-fold, respectively) vs. control subjects.
Here, we analyzed cells from the colon of IBD patients and show that Crohn's disease (CD) patients had significantly elevated numbers of IL-17+, CD4+ cells compared with healthy controls and ulcerative colitis (UC) patients, but these numbers did not vary based on the inflammatory status of the mucosa.
However, given the complexity and probably the redundancy of pathways leading to IBD lesions, and the fact that Th17 cells may also have protective functions, neutralization of IL-17Afailed to induce any improvement in CD.