title: Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity.
abstract: Interleukin-23 (IL-23) plays an essential role in driving intestinal pathology in experimental models of both T-cell-dependent and innate colitis. Furthermore, genome-wide association studies have identified several single-nucleotide polymorphisms in the IL-23 receptor (IL-23R) gene that are associated with either susceptibility or resistance to inflammatory bowel disease in humans. Although initially found to support the expansion and maintenance of CD4(+) T helper 17 (Th17) cells, IL-23 is now recognized as having multiple effects on the immune response, including restraining Foxp3(+) regulatory T-cell activity and inducing the expression of Th17-type cytokines from non-T-cell sources. Here we focus on Th17 cells and their associated cytokines IL-17A, IL-17F, IL-21 and IL-22. We review studies performed in mouse models of colitis where these effector cytokines have been shown to have either a pathogenic or a tissue-protective function. We also discuss the heterogeneity found within the Th17 population and the phenomenon of plasticity of Th17 cells, in particular the ability of these lymphocytes to extinguish IL-17 expression and turn on interferon-γ production to become Th1-like 'ex-Th17' cells. Interleukin-23 has been identified as a key driver in this process, and this may be an additional mechanism by which IL-23 promotes pathology in the intestinal tract. These 'ex-Th17' cells may contribute to disease pathogenesis through their secretion of pro-inflammatory mediators.
authors.affiliation: Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, UK. marika.kullberg@york.ac.uk
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Morrison
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Ballantyne
authors.forename: Marika C
authors.initials: MC
authors.lastname: Kullberg
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D007422:Intestines / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology*
chemical_list: D053759:Interleukin-23