Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa

Salvati, V. M.; Mazzarella, G.; Gianfrani, C.; Levings, M. K.; Stefanile, R.; De Giulio, B.; Laquinto, G.; Giardullo, N.; Auricchio, S.; Roncorolo, M. G.; Troncone, R.
January 2005
Gut;Jan2005, Vol. 54 Issue 1, p46
Academic Journal
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 enteropathles (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 γ (IFN-γ) 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-γ. Results: In untreated CD and NCE, 11-10 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-γ response to gliadin. Conclusions: rhIL-10 suppresses gliadin specific T cell activation. It may interfere with the antigen presenting capacily 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.


Related Articles

  • The cytokine interleukin 21: a new player in coeliac disease? Meresse, Bertrand; Verdier, Julien; Cerf-Bensussan, Nadine // Gut;Jul2008, Vol. 57 Issue 7, p879 

    The article presents a study which focuses on the use of single-nucleotide polymorphisms. In this context, researchers demonstrate that interleukin 21 (IL21) expression is increased in the intestinal mucosa of patients with active coeliac disease (CD) but not that of treated patients. It has...

  • Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease. Fina, D.; Sarra, M.; Caruso, R.; Del Vecchio Blanco, G.; Pallone, F.; MacDonald, T. T.; Monteleone, G. // Gut;Jul2008, Vol. 57 Issue 7, p887 

    Background: In coeliac disease (CD), the upper bowel lesion is associated with a marked infiltration of the mucosa with Thi cells secreting interferon γ (IFNγ) and expressing the Th1-associated transcription factor, T-bet. However, the molecular mechanisms which regulate T- bet and promote...

  • Local Challenge on Oral Mucosa With an α-Gliadin Related Synthetic Peptide in Patients With Celiac Disease. Lähteenoja, Hannu; Mäki, Markku; Viander, Markku; Räihä, Ismo; Vilja, Pekka; Rantala, Immo; Toivanen, Auli; Syrjänen, Stina // American Journal of Gastroenterology;Oct2000, Vol. 95 Issue 10, p2880 

    OBJECTIVE: Gluten-derived peptides (e.g., amino-acids 31-49 of α-gliadin) have been shown to cause changes typical of celiac disease in the gut. Gluten-derived peptides have mostly been used in in vitro studies. The easiest access to the gastrointestinal system may be the mouth. In...

  • Celiac disease: role of intestinal compartments in the mucosal immune response. Iacomino, Giuseppe; Marano, Angela; Stillitano, Ilaria; Aufiero, Vera; Iaquinto, Gaetano; Schettino, Michele; Masucci, Armando; Troncone, Riccardo; Auricchio, Salvatore; Mazzarella, Giuseppe // Molecular & Cellular Biochemistry;Jan2016, Vol. 411 Issue 1/2, p341 

    Different approaches have been used to study the pattern of cytokines in celiac disease (CD). Laser capture microdissection (LCM) is a powerful tool for the isolation of specific tissue compartments. We aimed to investigate the mucosal immune response that takes place in different intestinal...

  • Methylprednisolone inhibits interleukin-17 and interferon-gamma expression by both naive and primed T cells. Momčilović, Miljana; Miljković, Željka; Popadić, Dušan; Marković, Miloš; Savić, Emina; Ramić, Zorica; Miljković, Djordje; Mostarica-Stojković, Marija // BMC Immunology;2008, Vol. 9, Special section p1 

    Background: Interleukin-17 (IL-17)-producing cells are increasingly considered to be the major pathogenic population in various autoimmune disorders. The effects of glucocorticoids, widely used as therapeutics for inflammatory and autoimmune disorders, on IL-17 generation have not been...

  • The Role of Cellular Senescence in the Gastrointestinal Mucosa. Penfield, Joshua D.; Anderson, Marlys; Lutzke, Lori; Wang, Kenneth K. // Gut & Liver;May2013, Vol. 7 Issue 3, p270 

    Cellular senescence is a biologically irreversible state of cell-growth arrest that occurs following either a replicative or an oncogenic stimulus. This phenomenon occurs as a response to the presence of premalignant cells and appears to be an important anticancer mechanism that keeps these...

  • Gliadin Peptides as Triggers of the Proliferative and Stress/Innate Immune Response of the Celiac Small Intestinal Mucosa. Barone, Maria Vittoria; Troncone, Riccardo; Auricchio, Salvatore // International Journal of Molecular Sciences;2014, Vol. 15 Issue 11, p20518 

    Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin...

  • Clinical, HLA, and Small Bowel Immunohistochemical Features of Children with Positive Serum Antiendomysium Antibodies and Architecturally Normal Small Intestinal Mucosa. Paparo, Francesco; Petrone, Emma; Tosco, Antonella; Maglio, Maria; Borrelli, Melissa; Salvati, Virginia M.; Miele, Erasmo; Greco, Luigi; Auricchio, Salvatore; Troncone, Riccardo // American Journal of Gastroenterology;Oct2005, Vol. 100 Issue 10, p2294 

    BACKGROUND: Antiendomysium antibodies have a high sensitivity and specificity for celiac disease. A small percentage of subjects positive for these antibodies have a small intestinal mucosa hitherto considered normal. OBJECTIVES: The aim of this study was to characterize the clinical,...

  • Interleukin 15 controls the generation of the restricted T cell receptor repertoire of γδ intestinal intraepithelial lymphocytes. Hang Zhao; Hai Nguyen; Joonsoo Kang // Nature Immunology;Dec2005, Vol. 6 Issue 12, p1263 

    The γδ T cells are prevalent in the mucosal epithelia and are postulated to act as 'sentries' for maintaining tissue integrity. What these γδ T cells recognize is poorly defined, but given the restricted T cell receptor (TCR) repertoire, the idea that they are selected by self...


Read the Article


Sign out of this library

Other Topics