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Contributo in rivista
Tipo: Articolo in rivista
Titolo: IL-15 interferes with suppressive activity of intestinal regulatory T cells expanded in celiac disease.
Anno di pubblicazione: 2011
Autori: Delia Zanzi , MS 1 , 2 , 5 , Rosita Stefanile , PhD 3 , 5 , Sara Santagata , PhD 1 , Laura Iaffaldano , MS 1 , Gaetano Iaquinto , MD 4 , Nicola Giardullo , MD 4 , Giuliana Lania , MS 1 , Ilaria Vigliano , MS 1 , Aufi ero Rotondi Vera , BS 3 , Katia Ferrara , BS 1 , Salvatore Auricchio , MD 1 , 2 , Riccardo Troncone , MD 1 , 2 and Giuseppe Mazzarella , MS 2 , 3
Affiliazioni autori: 1 Department of Paediatrics University Federico II , Naples , Italy ; 2 European Laboratory for the Investigation of Food-Induced Diseases, University Federico II , Naples , Italy ; 3 Institute of Food Science, CNR, Immunobiology , Avellino , Italy ; 4 Gastroenterology and Digestive Endoscopy Service, San G. Moscati Hospital , Avellino , Italy ; 5 These authors contributed equally to this manuscript and should be considered joint fi rst authors . Correspondence: Giuseppe Mazzarella , MS, Institute of Food Science, CNR, Immunobiology , via Roma 64, Avellino , Italy .
Abstract: OBJECTIVES: Celiac disease (CD) is a condition in which the regulation of the mucosal immune response to dietary gliadin might be altered. The transcription factor forkhead box P3 (Foxp3) has been identifi ed as a marker of a subset of regulatory T cells (Treg). In this study, we have investigated the presence and the suppressive function of Treg cells in the celiac small intestinal mucosa, their correlation with the disease state, and the inducibility by gliadin in an organ culture system; moreover, we tried to defi ne whether interleukin 15 (IL-15), overexpressed in CD, could infl uence the regulatory activity of such cells. METHODS: The expression of Foxp3, CD3, CD4, and CD8 were analyzed by immunohistochemistry and fl ow cytometry in duodenal biopsies taken from patients with untreated CD, treated CD, and from non-CD controls, as well as in vitro cultured biopsy samples from treated CD patients, upon challenge with gliadin. Furthermore, we analyzed the suppressive function of CD4 + CD25 + T cells, isolated from untreated CD biopsy samples, on autologous responder CD4 + CD25 - T cells, in the presence of a polyclonal stimulus, with or without IL-15. RESULTS: Higher density of CD4 + CD25 + Foxp3 + T cells was seen in duodenal biopsy samples from active CD patients in comparison with treated CD and non-CD controls. In coculture, CD4 + CD25 + T cells were functionally suppressive, but their activity was impaired by IL-15. Cells from CD subjects showed increased sensitivity to the IL-15 action, likely due to enhanced expression of IL-15 receptor. Finally, we demonstrated an expansion of Foxp3 in treated CD mucosa following in vitro challenge with gliadin. CONCLUSIONS: These data suggest that CD4 + CD25 + Foxp3 + T cells are induced in situ by gliadin. However, their suppressor capacity might be impaired in vivo by IL-15; this phenomenon contributes to maintain and expand the local infl ammatory response in CD.
Lingua abstract: inglese
Pagine da: 1308
Pagine a: 1317
Pagine totali: 10
The American journal of gastroenterology
National Gastroenterological Association,
Numero volume: 106
Numero fascicolo: 7
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