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Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa.
Gut. 2005 Jan; 54(1):46-53.Gut

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.

Authors+Show Affiliations

Department of Paediatrics, University Federico II, Via Pansini, No 5, 80131 Naples, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15591503

Citation

Salvati, V M., et al. "Recombinant Human Interleukin 10 Suppresses Gliadin Dependent T Cell Activation in Ex Vivo Cultured Coeliac Intestinal Mucosa." Gut, vol. 54, no. 1, 2005, pp. 46-53.
Salvati VM, Mazzarella G, Gianfrani C, et al. Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa. Gut. 2005;54(1):46-53.
Salvati, V. M., Mazzarella, G., Gianfrani, C., Levings, M. K., Stefanile, R., De Giulio, B., Iaquinto, G., Giardullo, N., Auricchio, S., Roncarolo, M. G., & Troncone, R. (2005). Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa. Gut, 54(1), 46-53.
Salvati VM, et al. Recombinant Human Interleukin 10 Suppresses Gliadin Dependent T Cell Activation in Ex Vivo Cultured Coeliac Intestinal Mucosa. Gut. 2005;54(1):46-53. PubMed PMID: 15591503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa. AU - Salvati,V M, AU - Mazzarella,G, AU - Gianfrani,C, AU - Levings,M K, AU - Stefanile,R, AU - De Giulio,B, AU - Iaquinto,G, AU - Giardullo,N, AU - Auricchio,S, AU - Roncarolo,M G, AU - Troncone,R, PY - 2004/12/14/pubmed PY - 2005/2/3/medline PY - 2004/12/14/entrez SP - 46 EP - 53 JF - Gut JO - Gut VL - 54 IS - 1 N2 - 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. SN - 0017-5749 UR - https://www.unboundmedicine.com/medline/citation/15591503/Recombinant_human_interleukin_10_suppresses_gliadin_dependent_T_cell_activation_in_ex_vivo_cultured_coeliac_intestinal_mucosa_ L2 - https://gut.bmj.com/lookup/pmidlookup?view=long&pmid=15591503 DB - PRIME DP - Unbound Medicine ER -