AhR is down-regulated in intestinal tissue of patients with IBD; AhR signaling, via IL-22, inhibits inflammation and colitis in the gastrointestinal tract of mice. AhR-related compounds might be developed to treat patients with IBDs.

Gut inflammation occurring in patients with Crohn's disease and patients with ulcerative colitis has been traditionally associated with an exaggerated Th1 or Th2 cell response, respectively. However, recent studies have shown that in both inflammatory bowel diseases (IBD) there is also enhanced synthesis of cytokines made by a distinct subset of T helper cells, termed Th17 cells. The discovery that this new T-cell subset drives immune-mediated pathology in the gut, and that interleukin (IL)-23 amplifies Th17 cell responses and gut inflammation, has contributed to elucidate new pathways of tissue damage as well as to open new avenues for development of therapeutic strategies in IBD. Nonetheless, it has been recently shown that Th17-related cytokines, such as IL-17A and IL-22, can exert protective rather than detrimental effects in the gut. We here review the available data regarding the role of Th17 cells and IL-23 in chronic intestinal inflammation.

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T cells are crucial mediators of the skin damage in psoriasis. We here show that interleukin-21 (IL-21), a T cell-derived cytokine, is highly expressed in the skin of individuals with psoriasis, stimulates human keratinocytes to proliferate and causes epidermal hyperplasia when injected intradermally into mice. In the human psoriasis xenograft mouse model, blockade of IL-21 activity resolves inflammation and reduces keratinocyte proliferation. Blocking IL-21 may represent a new therapeutic strategy in psoriasis.

IL-21 expression is increased in the gut of patients with colitis-associated colon cancer, and genetic ablation or antibody neutralization of IL-21 reduces tumor size and inflammation in mice treated with dextran sulfate sodium and azoxymethane.

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IL21 is overproduced in the mucosa of CD patients, where it helps sustain T-bet expression and IFNgamma production.

Helicobacter pylori (Hp) infection is associated with a marked infiltration of the gastric mucosa by inflammatory cells. The molecular pathways that control Hp-associated inflammatory reaction are complex, but locally induced cytokines seem to contribute to maintaining the ongoing inflammation. We have previously shown that IL-17 is over-produced in Hp-infected gastric mucosa, and that IL-17 stimulates the synthesis of IL-8, the major neutrophil chemoattractant. Factors/mechanisms that regulate IL-17 expression remain, however, unknown. In this study, we initially expanded our previous data, showing that CD4(+) and CD8(+) T cells are a source of IL-17 in Hp-infected samples. Since IL-23 enhances T cell-derived IL-17 during bacterial infections, we then assessed the role of IL-23 in controlling IL-17 expression in Hp-colonized stomach. Using real-time PCR and ELISA, IL-23 was detected in all gastric biopsies, but its expression was more pronounced in Hp-infected samples in comparison to controls. Treatment of normal gastric lamina propria mononuclear cells (LPMC) with IL-23 enhanced Stat3 activation and IL-17 secretion, and pharmacological inhibition of Stat3 prevented IL-23-driven IL-17 synthesis. Consistently, blockade of IL-23 in cultures of LPMC from Hp-infected patients reduced Stat3 activation and IL-17 production. Data show that IL-23 is overexpressed in Hp-infected gastric mucosa where it could contribute to sustaining IL-17 production.