title: Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes.
abstract: 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.
authors.affiliation: Division of Paediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: A I
authors.initials: AI
authors.lastname: Lahdenperä
authors.forename: V
authors.initials: V
authors.lastname: Hölttä
authors.forename: T
authors.initials: T
authors.lastname: Ruohtula
authors.forename: H M
authors.initials: HM
authors.lastname: Salo
authors.forename: L
authors.initials: L
authors.lastname: Orivuori
authors.forename: M
authors.initials: M
authors.lastname: Westerholm-Ormio
authors.forename: E
authors.initials: E
authors.lastname: Savilahti
authors.forename: K
authors.initials: K
authors.lastname: Fälth-Magnusson
authors.forename: L
authors.initials: L
authors.lastname: Högberg
authors.forename: J
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: O
authors.initials: O
authors.lastname: Vaarala
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D017209:Apoptosis / Q000235:genetics; D001284:Atrophy; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003110:Colonic Neoplasms / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D055050:Diet, Gluten-Free; D004386:Duodenum / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D019204:GTP-Binding Proteins; D006801:Humans; D007223:Infant; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008297:Male; D008871:Microvilli / Q000648:ultrastructure; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D011503:Transglutaminases / Q000276:immunology; D015854:Up-Regulation
chemical_list: D001323:Autoantibodies; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508717:IL17A protein, human; D020381:Interleukin-17; D012333:RNA, Messenger; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins