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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa.
Anno di pubblicazione: 2005
Formato: Elettronico Cartaceo
Autori: Salvati V.M.; Mazzarella G.; Gianfrani C.; Levings M.K.; Stefanile R; De Giulio B.; Iaquinto G; Giardullo ; Auricchio S.; Roncarolo M.G.; Troncone R.
Affiliazioni autori: Department of Paediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy Institute of Food, Science, and Technology, CNR Avellino, Italy San Raffaele Telethon Institute of Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy Gastroenterology and Endoscopy Unit Hospital, ''San Giuseppe Moscati'', Avellino, Italy Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
Abstract: BACKGROUND: Enteropathy in coeliac disease (CD) is sustained by a gliadin specific Th1 response. Interleukin (IL)-10 can downregulate Th1 immune responses. AIM: We investigated the ability of recombinant human (rh) IL-10 to suppress gliadin induced Th1 response. PATIENTS AND METHODS: IL-10 RNA transcripts were analysed by competitive reverse transcription-polymerase chain reaction in duodenal biopsies from untreated and treated CD patients, non-coeliac enteropathies (NCE), and controls. CD biopsies were cultured with a peptic-tryptic digest of gliadin with or without rhIL-10. The proportion of CD80+ and CD25+ cells in the lamina propria, epithelial expression of Fas, intraepithelial infiltration of CD3+ cells, as well as cytokine synthesis (interferon gamma (IFN-gamma) and IL-2) were measured. Short term T cell lines (TCLs) obtained from treated CD biopsies cultured with gliadin with or without rhIL-10 were analysed by ELISPOT for gliadin specific production of IFN-gamma. RESULTS: In untreated CD and NCE, IL-10 RNA transcripts were significantly upregulated. In ex vivo organ cultures, rhIL-10 downregulated gliadin induced cytokine synthesis, inhibited intraepithelial migration of CD3+ cells, and reduced the proportion of lamina propria CD25+ and CD80+ cells whereas it did not interfere with epithelial Fas expression. In short term TCLs, rhIL-10 abrogated the IFN-gamma response to gliadin. CONCLUSIONS: rhIL-10 suppresses gliadin specific T cell activation. It may interfere with the antigen presenting capacity of lamina propria mononuclear cells as it reduces the expression of CD80. Interestingly, rhIL-10 also induces a long term hyporesponsiveness of gliadin specific mucosal T cells. These results offer new perspectives for therapeutic strategies in coeliac patients based on immune modulation by IL-10.
Lingua abstract: inglese
Pagine da: 46
Pagine a: 53
British Medical Association,
Numero volume: 54
Referee: Sė: Internazionale
Altre informazioni: 29
Allegati: Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa
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