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.

Recombinant human IL-10 suppreses gliadin-dependent T-cell activation in ex vivo cultured celiac intestinal mucosa / Salvati, VIRGINIA MICHELA; Mazzarella, G; Gianfrani, C; Levings, M; Stefanile, R; DE GIULIO, B; Iaquinto, G; Giardullo, N; Auricchio, Salvatore; Roncarolo, M; Troncone, Riccardo. - In: GUT. - ISSN 0017-5749. - STAMPA. - 54:(2005), pp. 46-53. [10.1136/gut.2003.023150]

Recombinant human IL-10 suppreses gliadin-dependent T-cell activation in ex vivo cultured celiac intestinal mucosa.

SALVATI, VIRGINIA MICHELA;AURICCHIO, SALVATORE;TRONCONE, RICCARDO
2005

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.
2005
GUT
Recombinant human IL-10 suppreses gliadin-dependent T-cell activation in ex vivo cultured celiac intestinal mucosa / Salvati, VIRGINIA MICHELA; Mazzarella, G; Gianfrani, C; Levings, M; Stefanile, R; DE GIULIO, B; Iaquinto, G; Giardullo, N; Auricchio, Salvatore; Roncarolo, M; Troncone, Riccardo. - In: GUT. - ISSN 0017-5749. - STAMPA. - 54:(2005), pp. 46-53. [10.1136/gut.2003.023150]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/202017
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