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- Title
Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes.
- Authors
Lahdenperä, A. I.; Hölttä, V.; Ruohtula, T.; Salo, H. M.; Orivuori, L.; Westerholm-Ormio, M.; Savilahti, E.; Fälth-Magnusson, K.; Högberg, L.; Ludvigsson, J.; Vaarala, O.
- Abstract
Summary Up-regulation of interleukin (IL)-17 in small intestinal mucosa has been reported in coeliac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL-17 immunity in different stages of CD, including transglutaminase antibody (TGA)-positive children with potential CD, children with untreated and gluten-free diet-treated CD and in children with T1D. Immunohistochemistry was used for identification of IL-17 and forkhead box protein 3 (FoxP3)-positive cells and quantitative polymerase chain reaction (qPCR) for IL-17, FoxP3, retinoic acid-related orphan receptor (ROR)c and interferon (IFN)-γ transcripts. IL-1β, IL-6 and IL-17 were studied in supernatants from biopsy cultures. Expression of the apoptotic markers BAX and bcl-2 was evaluated in IL-17-stimulated CaCo-2 cells. The mucosal expression of IL-17 and FoxP3 transcripts were elevated in individuals with untreated CD when compared with the TGA-negative reference children, children with potential CD or gluten-free diet-treated children with CD ( P < 0·005 for all IL-17 comparisons and P < 0·01 for all FoxP3 comparisons). The numbers of IL-17-positive cells were higher in lamina propria in children with CD than in children with T1D ( P < 0·05). In biopsy specimens from patients with untreated CD, enhanced spontaneous secretion of IL-1β, IL-6 and IL-17 was seen. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17 could, however, serve as a biomarker for the development of villous atrophy and active CD.
- Subjects
CELIAC disease; TYPE 1 diabetes; INTERLEUKIN-17; IMMUNITY; SMALL intestine; IMMUNOHISTOCHEMISTRY; TRANSGLUTAMINASES; MUCOUS membranes; GENE expression
- Publication
Clinical & Experimental Immunology, 2012, Vol 167, Issue 2, p226
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/j.1365-2249.2011.04510.x