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Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease

Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease
Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease
Objective
The short isoform of thymic stromal lymphopoietin (TSLP), a cytokine constitutively expressed by epithelial cells, is crucial in preserving immune tolerance in the gut. TSLP deficiency has been implicated in sustaining intestinal damage in Crohn's disease. We explored mucosal TSLP expression and function in refractory and uncomplicated coeliac disease (CD), a T-cell-mediated enteropathy induced by gluten in genetically susceptible individuals.
Design
TSLP isoforms-long and short-and receptors -TSLPR and interleukin (IL)-7Rα -were assessed by immunofluorescence, immunoblotting and αRT-PCR in the duodenum of untreated, treated, potential and refractory patients with CD. The ability of the serine protease furin or CD biopsy supernatants to cleave TSLP was evaluated by immunoblotting. The production of interferon (IFN)-γ and IL-8 by untreated CD biopsies cultured ex vivo with TSLP isoforms was also assessed.
Results
Mucosal TSLP, but not TSLPR and IL-7Rα, was reduced in untreated CD and refractory CD in comparison to treated CD, potential CD and controls. Transcripts of both TSLP isoforms were decreased in active CD mucosa. Furin, which was overexpressed in active CD biopsies, was able to cleave TSLP in vitro. Accordingly, refractory and untreated CD supernatants showed higher TSLP-degrading capacity in comparison to treated CD and control supernatants. In our ex vivo model, both TSLP isoforms significantly downregulated IFN-γ and IL-8 production by untreated CD biopsies.
Conclusions
Reduced mucosal TSLP expression may contribute to intestinal damage in refractory and untreated CD. Further studies are needed to verify whether restoring TSLP might be therapeutically useful especially in refractory patients with CD.
0017-5749
1670-1680
Biancheri, Paolo
479c256d-187d-4b65-b226-8069299e61b2
Di Sabatino, Antonio
08cb3ec3-e4a0-423c-aa27-f428979b957d
Rescigno, Maria
2d911b28-131f-4096-9b04-d1f734fec6d2
Giuffrida, Paolo
7089a195-db88-4489-8c00-638a9cc61fd5
Fornasa, Giulia
68454e0e-d3cf-4b20-af9e-fffabee2b767
Tsilingiri, Katerina
5619e4b7-6b4a-432d-a38b-a48337e9e08f
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Papadia, Cinzia
8826814a-5914-4ad6-b2e6-6ceb63c9191a
Wood, Eleanor
87757ec7-3a16-43b5-91fa-00899bf122ec
Pasini, Alessandra
06c34153-b02d-4d2d-98eb-58350259775d
Ubezio, Cristina
23a4ee4b-1e2c-4001-8e84-034731dce514
Vanoli, Alessandro
bb1a3645-539c-4201-ba3d-987222c1ce2a
Forbes, Alastair
af1986ca-4ac9-4dfd-9b66-106c8e81acf9
MacDonald, Thomas
8f131c33-d168-44e9-8de8-59c717868931
Corazza, Gino
82a752f4-c188-4057-bf2d-2845acf1f3e4
Biancheri, Paolo
479c256d-187d-4b65-b226-8069299e61b2
Di Sabatino, Antonio
08cb3ec3-e4a0-423c-aa27-f428979b957d
Rescigno, Maria
2d911b28-131f-4096-9b04-d1f734fec6d2
Giuffrida, Paolo
7089a195-db88-4489-8c00-638a9cc61fd5
Fornasa, Giulia
68454e0e-d3cf-4b20-af9e-fffabee2b767
Tsilingiri, Katerina
5619e4b7-6b4a-432d-a38b-a48337e9e08f
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Papadia, Cinzia
8826814a-5914-4ad6-b2e6-6ceb63c9191a
Wood, Eleanor
87757ec7-3a16-43b5-91fa-00899bf122ec
Pasini, Alessandra
06c34153-b02d-4d2d-98eb-58350259775d
Ubezio, Cristina
23a4ee4b-1e2c-4001-8e84-034731dce514
Vanoli, Alessandro
bb1a3645-539c-4201-ba3d-987222c1ce2a
Forbes, Alastair
af1986ca-4ac9-4dfd-9b66-106c8e81acf9
MacDonald, Thomas
8f131c33-d168-44e9-8de8-59c717868931
Corazza, Gino
82a752f4-c188-4057-bf2d-2845acf1f3e4

Biancheri, Paolo, Di Sabatino, Antonio, Rescigno, Maria, Giuffrida, Paolo, Fornasa, Giulia, Tsilingiri, Katerina, Pender, Sylvia L.F., Papadia, Cinzia, Wood, Eleanor, Pasini, Alessandra, Ubezio, Cristina, Vanoli, Alessandro, Forbes, Alastair, MacDonald, Thomas and Corazza, Gino (2016) Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease. Gut, 65 (10), 1670-1680. (doi:10.1136/gutjnl-2014-308876).

Record type: Article

Abstract

Objective
The short isoform of thymic stromal lymphopoietin (TSLP), a cytokine constitutively expressed by epithelial cells, is crucial in preserving immune tolerance in the gut. TSLP deficiency has been implicated in sustaining intestinal damage in Crohn's disease. We explored mucosal TSLP expression and function in refractory and uncomplicated coeliac disease (CD), a T-cell-mediated enteropathy induced by gluten in genetically susceptible individuals.
Design
TSLP isoforms-long and short-and receptors -TSLPR and interleukin (IL)-7Rα -were assessed by immunofluorescence, immunoblotting and αRT-PCR in the duodenum of untreated, treated, potential and refractory patients with CD. The ability of the serine protease furin or CD biopsy supernatants to cleave TSLP was evaluated by immunoblotting. The production of interferon (IFN)-γ and IL-8 by untreated CD biopsies cultured ex vivo with TSLP isoforms was also assessed.
Results
Mucosal TSLP, but not TSLPR and IL-7Rα, was reduced in untreated CD and refractory CD in comparison to treated CD, potential CD and controls. Transcripts of both TSLP isoforms were decreased in active CD mucosa. Furin, which was overexpressed in active CD biopsies, was able to cleave TSLP in vitro. Accordingly, refractory and untreated CD supernatants showed higher TSLP-degrading capacity in comparison to treated CD and control supernatants. In our ex vivo model, both TSLP isoforms significantly downregulated IFN-γ and IL-8 production by untreated CD biopsies.
Conclusions
Reduced mucosal TSLP expression may contribute to intestinal damage in refractory and untreated CD. Further studies are needed to verify whether restoring TSLP might be therapeutically useful especially in refractory patients with CD.

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More information

Accepted/In Press date: 23 June 2015
e-pub ahead of print date: 4 September 2015
Published date: 1 October 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 378948
URI: http://eprints.soton.ac.uk/id/eprint/378948
ISSN: 0017-5749
PURE UUID: dd46bb74-a060-4799-8653-a8951b8a9ac7
ORCID for Sylvia L.F. Pender: ORCID iD orcid.org/0000-0001-6332-0333

Catalogue record

Date deposited: 18 Jul 2015 15:04
Last modified: 17 Jan 2020 17:30

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Contributors

Author: Paolo Biancheri
Author: Antonio Di Sabatino
Author: Maria Rescigno
Author: Paolo Giuffrida
Author: Giulia Fornasa
Author: Katerina Tsilingiri
Author: Cinzia Papadia
Author: Eleanor Wood
Author: Alessandra Pasini
Author: Cristina Ubezio
Author: Alessandro Vanoli
Author: Alastair Forbes
Author: Thomas MacDonald
Author: Gino Corazza

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