期刊
IMMUNOLOGY
卷 133, 期 4, 页码 397-408出版社
WILEY
DOI: 10.1111/j.1365-2567.2011.03454.x
关键词
colitis; inflammation; interferon-gamma; interleukin-17A; interleukin-23; T helper 17 cells
类别
资金
- Wellcome Trust
- Medical Research Council
- Crohn's in Childhood Research Association
- MRC [G0700806] Funding Source: UKRI
- Medical Research Council [G0700806] Funding Source: researchfish
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.
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