Article Text
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 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, 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-γ 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.
- CD, coeliac disease
- IL-10, interleukin 10
- rhIL-10, human recombinant IL-10
- NCE, non-coeliac enteropathy
- RT-PCR, reverse transcription-polymerase chain reaction
- TCL, T cell lines
- IFN-γ, interferon γ
- Tr1 cells, type 1 T regulatory cells
- TGF-β, transforming growth factor β
- LPT, lamina propria T cells
- IELs, intraepithelial lymphocytes
- PT, peptic-tryptic
- mAb, monoclonal antibody
- PBS, phosphate buffered saline
- tTG, tissue transglutaminase
- PBMCs, peripheral blood mononuclear cells
- SFC, spot forming cells
- interleukin 10
- coeliac disease
- immune suppression
- organ culture
- gliadin specific T cell lines
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- CD, coeliac disease
- IL-10, interleukin 10
- rhIL-10, human recombinant IL-10
- NCE, non-coeliac enteropathy
- RT-PCR, reverse transcription-polymerase chain reaction
- TCL, T cell lines
- IFN-γ, interferon γ
- Tr1 cells, type 1 T regulatory cells
- TGF-β, transforming growth factor β
- LPT, lamina propria T cells
- IELs, intraepithelial lymphocytes
- PT, peptic-tryptic
- mAb, monoclonal antibody
- PBS, phosphate buffered saline
- tTG, tissue transglutaminase
- PBMCs, peripheral blood mononuclear cells
- SFC, spot forming cells
Footnotes
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↵* Present address: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada