As disease normally resolved, neutralization of IL-22 caused luminal narrowing of the cecum-a feature reminiscent of fibrotic strictures seen in Crohn disease patients.
Our results do not support the hypothesis that anti-TNF<i>α</i> treatment has an early effect on the mucosal levels of IL-17A, IL-21, and IL-22 or LP T cell production of these cytokines in CD.
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.
IL-21 expression was most abundant in germinal centers (GCs) of the lymphoid aggregates, and IL-21R expression assessed semiquantitatively, was significantly higher in patients with CD compared to non-IBD controls.
In vitro treatment with IFX greatly promoted CD CD4+ T cells to express IL-22, which was inhibited by rhTACE, indicating that reverse signaling through binding to membrane-bound TNF mediates anti-TNF-induced IL-22 expression of CD CD4+ T cells.
Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel diseases (IBDs), are characterized by high levels of IL-22 production.
We showed activation of colonic IL-17/IL-22 axis and upregulation of FOXP3 to occur both in pediatric CD and in UC, indicating shared immunological characteristics.
In patients with CD, CD4+ T cells that express NKG2D produced high levels of interleukin (IL)-17 and IL-22 and expressed high levels of CCR6, the IL-23 receptor, CD161, and RORC (a transcription factor that regulates expression of Th17 cytokines).
Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10⁻⁵).
The Th17 cytokine IL-22 is expressed at high levels in CD and correlates with disease activity, offering a better separation between active and inactive CD than IL-6 and TNF-alpha.
Finally, we show that IL-21 positively regulates its own expression in human intestinal CD3(+) lamina propria lymphocytes, and blockade of endogenous IL-21 in cultures of CD3(+) lamina propria lymphocytes isolated from patients with Crohn's disease, a chronic inflammatory bowel disease characterized by high IL-21, down-regulates Stat3 activation and IL-21 expression.
To investigate the possible role of systemic IL-22 in CD, we then administered IL-22 to healthy mice and found an up-regulation of LPS-binding protein (LBP) blood levels reaching concentrations known to neutralize LPS.
IL-12 enhanced IL-21 in normal lamina propria lymphocytes through an IFN-gamma-independent mechanism, and blocking IL-12 in CD LPMCs decreased anti-CD3-stimulated IL-21 expression.