Mucosal cytokine network in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors and commensal bacteria is involved. The chronic inflammatory process leads to disruption of the epithelial barrier, and the formation of epithelial ulceration. This permits easy access for the luminal microbiota and dietary antigens to cells resident in the lamina propria, and stimulates further pathological immune cell responses. Cytokines are essential mediators of the interactions between activated immune cells and non-immune cells, including epithelial and mesenchymal cells. The clinical efficacy of targeting TNF-alpha clearly indicates that cytokines are the therapeutic targets in IBD patients. In this manuscript, we focus on the biological activities of recently-reported cytokines [Interleukin (IL)-17 cytokine family, IL-31 and IL-32], which might play a role through interaction with TNF-alpha in the pathophysiology of IBD.

Figure 1

Mucosal cytokine network mediated by IL-17A/F and TNF-α. TGF-β induces the differentiation of Th17cells from naive CD4+ T cells in the presence of IL-6, and full differentiation to Th17 cells is dependent on IL-23. The transcriptional factors required for the development of Th1 (STAT4 and T-bet) and Th2 (STAT6) cells are not required for the induction of Th17/ThIL-17 cells. IFN-γ also suppresses the differentiation of Th17 cells. IL-4 inhibits the development of Th17 cells. One of the important roles of IL-17A/F is the augmentation of the TNF-α-induced secretion of IL-6, a crucial factor for Th17 cell development.