Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease
- 1 December 2007
- Vol. 56 (12), 1696-1705
- https://doi.org/10.1136/gut.2006.116467
Abstract
Crohn's disease is a life-long form of inflammatory bowel disease (IBD) mediated by mucosal immune abnormalities. Understanding of the pathogenesis is limited because it is based on data from adults with chronic Crohn's disease. We investigated mucosal T-cell immunoregulatory events in children with early Crohn's disease. Mucosal biopsies and T-cell clones were derived from children experiencing the first attack of Crohn's disease, children with long-standing Crohn's disease, infectious colitis, and children without gut inflammation. As in acute infectious colitis, interleukin (IL) 12 induced T cells from early Crohn's disease to acquire a strongly polarised T helper (Th) type 1 response characterised by high IFN-gamma production and IL12Rbeta2 chain expression. Th1 polarisation was not induced in clones from late Crohn's disease. Mucosal levels of IL12p40 and IL12Rbeta2 messenger RNA were significantly higher in children with early than late Crohn's disease. These results demonstrate that susceptibility to IL12-mediated modulation is strongly dependent on the stage of Crohn's disease. At the onset of Crohn's disease mucosal T cells appear to mount a typical Th1 response that resembles an acute infectious process, and is lost with progression to late Crohn's disease. This suggests that mucosal T-cell immunoregulation varies with the course of human IBD. Patients with the initial manifestations of IBD may represent an ideal population in which immunomodulation may have optimal therapeutic efficacy.This publication has 63 references indexed in Scilit:
- Phenotypic and functional features of human Th17 cellsThe Journal of Experimental Medicine, 2007
- The IL-23/IL-17 axis in inflammationJCI Insight, 2006
- IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6JCI Insight, 2006
- Toll-like receptor 2 controls expansion and function of regulatory T cellsJCI Insight, 2006
- TH-17: a giant step from TH1 and TH2Nature Immunology, 2005
- Standardized determination of real-time PCR efficiency from a single reaction set-upNucleic Acids Research, 2003
- The Immunology of Mucosal Models of InflammationAnnual Review of Immunology, 2002
- The role of IL-12 in the induction of organ-specific autoimmune diseasesImmunology Today, 1995
- The role of interleukin 12 in the immune response, disease and therapyImmunology Today, 1994
- Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones.The Journal of Experimental Medicine, 1994