The interleukin-23 axis in intestinal inflammation.
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.
Ahern
Philip P
PP
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Izcue
Ana
A
Maloy
Kevin J
KJ
Powrie
Fiona
F
D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D020381:Interleukin-17; D053759:Interleukin-23