Up‐regulation of small intestinal interleukin‐17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes

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.