In the gut of patients with Crohn’s disease and patients with ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in humans,the tissue-damaging immune response is mediated by an active cross-talk between immune and non-immune cells.Accumulating evidence indicates also that cytokines produced by these cells play a major role in initiating and shaping this pathologic process.One such cytokine seems to be interleukin(IL)-21,a member of the common γ-chainreceptor family.IL-21 is produced in excess in the in-flamed intestine of patients with IBD mostly by activated CD4+ T helper cells co-expressing interferon-γ and follicular T helper cells.Moreover,both in vitro and in vivo studies indicate that excessive IL-21 production leads to the activation of multiple signaling pathways that expand and sustain the ongoing mucosal inflammation.In this article,we review the available data supporting the pathogenic role of IL-21 in IBD. In the gut of patients with Crohn’s disease and patients with ulcerative colitis, the major forms of inflammatory bowel diseases (IBD) in humans, the tissue-damaging immune response is mediated by an active cross-talk between immune and non-immune cells. Accumulating is shown that that cytokines produced by these cells play a major role in initiating and shaping this pathologic process. One such cytokine seems to be interleukin (IL) -21, a member of the common γ-chain receptor family. IL-21 is produced in excess in the in-flamed intestine of patients with IBD mostly by activated CD4 + T helper cells co-expressing interferon-γ and follicular T helper cells. Moreover, both in vitro and in vivo studies indicate that excessive IL-21 production leads to the activation of multiple signaling pathways that expand and sustain the ongoing mucosal inflammation. This article, we review the available data supporting the pathogenic role of IL-21 in IBD.