Th17 Cytokines in Inflammatory Bowel Diseases: Discerning the Good from the Bad

Abstract

T helper (Th) 17 cells are a branch of the CD4+ T cell compartment involved in host protection against bacterial and fungal infections as well as in orchestration of chronic inflammation and autoimmunity in many organs. Th17 cells produce interleukin (IL)-17A and variable amounts of IL-17F, IL-21, IL-22 and IL-26, under the regulation of retinoic-acid-related orphan receptors (ROR)-γt and ROR-α. Accumulating evidence supports the involvement of Th17 cells in the tissue-damaging immune response occurring in patients with Crohn's disease and patients with ulcerative colitis, the two major forms of inflammatory bowel disease (IBD) in human beings. However in the gut, Th17 cells can also have tissue-protective effects, mostly depending on their ability to enhance epithelial barrier function and counter-regulatory mechanisms. In this article, we summarize the available data on the dual role of Th17 cells in gut homeostasis and inflammation and discuss whether and how Th17 cytokine blockers can enter into the therapeutic armamentarium of IBD.

Keywords :

• Crohn's disease
• IL-17
• IL-21
• IL-23
• ulcerative colitis