IL-23/IL-17 immunity as a hallmark of Crohn's disease
Article first published online: 29 MAY 2008
Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 14, Issue 9, pages 1175–1184, September 2008
How to Cite
Hölttä, V., Klemetti, P., Sipponen, T., Westerholm-Ormio, M., Kociubinski, G., Salo, H., Räsänen, L., Kolho, K.-L., Färkkilä, M., Savilahti, E. and Vaarala, O. (2008), IL-23/IL-17 immunity as a hallmark of Crohn's disease. Inflamm Bowel Dis, 14: 1175–1184. doi: 10.1002/ibd.20475
- Issue published online: 5 AUG 2008
- Article first published online: 29 MAY 2008
- Manuscript Received: 5 MAR 2008
- Manuscript Accepted: 5 MAR 2008
- Academy of Finland
- Sigrid Juselius Foundation
- Finnish Cultural Foundation
- Foundation for Pediatric Research
- Th17 cell;
- Crohn's disease;
- inflammatory bowel disease;
Background: We studied the balance between ileal T-effector cells versus T-regulatory cells in active and inactive Crohn's disease (CD).
Methods: We compared effector and regulatory T-cell-related markers such as interleukin (IL)–17, interferon (IFN)-γ, IL-4, and Foxp3 transforming growth factor (TGF)–β CTLA-4 and markers for innate immune activation such as IL-6, IL-10, IL-18, IL-23, tumor necrosis factor (TNF)–α, and IL-12p70, studied with immunohistochemistry and RT-PCR in ileal biopsies from patients with active or inactive CD and from control subjects. IL-17 in fecal samples was detected by ELISA. The effect of IL-17 on IL-8 and TNF-α mRNA expression in epithelial cell line Caco-2 was studied.
Results: The numbers of IL-4-, IL-17-, and IL-23(p19)-positive cells in the lamina propria were higher in patients with CD, both active and inactive, than in the controls. mRNA expression of IL-17A, IL-6, and Foxp3 was increased in the biopsies both from patients with active disease and those in remission, whereas mRNA expression of IL-23 was increased only in active disease. Fecal IL-17 concentration was increased in patients with active disease. IL-17 enhanced the IL-8 and TNF-α response of the epithelial cell line to lipopolysaccharide (LPS) in vitro.
Conclusions: Our findings suggest that activation of the IL-23/IL-17 axis is fundamentally connected to the etiology of CD and may represent the basis for the relapsing nature of the disease by increasing the sensitivity of epithelium to microbial LPS.
(Inflamm Bowel Dis 2008)