The interleukin-23 axis in intestinal inflammation.
Ahern PP., Izcue A., Maloy KJ., Powrie F.
Immune responses in the intestine are tightly regulated to ensure host protective immunity in the absence of immune pathology. Interleukin-23 (IL-23) has recently been shown to be a key player in influencing the balance between tolerance and immunity in the intestine. Production of IL-23 is enriched within the intestine and has been shown to orchestrate T-cell-dependent and T-cell-independent pathways of intestinal inflammation through effects on T-helper 1 (Th1) and Th17-associated cytokines. Furthermore, IL-23 restrains regulatory T-cell responses in the gut, favoring inflammation. Polymorphisms in the IL-23 receptor have been associated with susceptibility to inflammatory bowel diseases (IBDs) in humans, pinpointing the IL-23 axis as a key, conserved pathway in intestinal homeostasis. In addition to its role in dysregulated inflammatory responses, there is also evidence that IL-23 and the Th17 axis mediate beneficial roles in host protective immunity and barrier function in the intestine. Here we discuss the dual roles of IL-23 in intestinal immunity and how IL-23 and downstream effector pathways may make novel targets for the treatment of IBD.