Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity
Open Access
- 2 June 2011
- journal article
- review article
- Published by Wiley in Immunology
- Vol. 133 (4), 397-408
- https://doi.org/10.1111/j.1365-2567.2011.03454.x
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-gamma 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.Keywords
This publication has 153 references indexed in Scilit:
- Functional Specialization of Interleukin-17 Family MembersImmunity, 2011
- Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T CellsImmunity, 2010
- Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and HomeostasisImmunity, 2010
- Induction of Intestinal Th17 Cells by Segmented Filamentous BacteriaCell, 2009
- Regulatory T Cells Reinforce Intestinal HomeostasisImmunity, 2009
- Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cellsEuropean Journal of Immunology, 2009
- Specific Microbiota Direct the Differentiation of IL-17-Producing T-Helper Cells in the Mucosa of the Small IntestineCell Host & Microbe, 2008
- The Biological Functions of T Helper 17 Cell Effector Cytokines in InflammationImmunity, 2008
- Interleukin-23 Restrains Regulatory T Cell Activity to Drive T Cell-Dependent ColitisImmunity, 2008
- T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγImmunity, 2008