Increased expression of mucosal addressin cell adhesion molecule 1 in the duodenum of patients with active celiac disease is associated with depletion of integrin α4β7-positive T cells in blood

Antonio Di Sabatino, Laura Rovedatti, Manuela M. Rosado, Rita Carsetti, Gino R. Corazza, Thomas T. MacDonald

Research output: Contribution to journalArticlepeer-review

Abstract

Mucosal addressin cell adhesion molecule 1, expressed on gut endothelial cells, in conjunction with integrin α4β7, expressed on lymphocytes, is critical in lymphocyte homing to the gut. The mucosal addressin cell adhesion molecule 1/integrin α4β7 pathway is involved in the pathogenesis of chronic intestinal inflammation by recruiting lymphocytes into inflamed gut. We explored the duodenal expression of mucosal addressin cell adhesion molecule 1 and the peripheral T-cell expression of integrin α4β7 in patients with celiac disease. Duodenal biopsies and a peripheral blood sample were collected from 15 celiac patients, before and after 12 months of gluten-free diet, and from 12 control subjects. Treated celiac biopsies were cultured with peptic-tryptic digest of gliadin and/or an anti-interferon α neutralizing antibody. Mucosal addressin cell adhesion molecule 1 was determined by confocal immunofluorescence microscopy and immunoblotting. Integrin β7-positive T cells were analyzed by flow cytometry. Mucosal addressin cell adhesion molecule 1 expression was significantly higher in active celiac disease than in normal mucosa. After gluten-free diet, a dramatic reduction of mucosal addressin cell adhesion molecule 1 was also observed. No difference was seen between patients with celiac disease after treatment and controls. Ex vivo peptic-tryptic digest of gliadin challenge induced a marked increase of mucosal addressin cell adhesion molecule 1 expression. Blocking interferon α inhibited the peptic-tryptic digest of gliadin-induced mucosal addressin cell adhesion molecule 1 overexpression. The percentage of circulating β7-positive T cells was significantly lower in untreated celiac disease in comparison to controls but normalized after gluten-free diet. Mucosal addressin cell adhesion molecule 1 is strongly up-regulated in active celiac disease dependent on interferon α and is associated with peripheral depletion of integrin α4β7-expressing T cells. We conclude that mucosal addressin cell adhesion molecule 1 may represent an important determinant for the generation of mucosal damage in celiac disease.

Original languageEnglish
Pages (from-to)699-704
Number of pages6
JournalHuman Pathology
Volume40
Issue number5
DOIs
Publication statusPublished - May 2009

Keywords

  • Gliadin
  • Homing
  • Interferon-α
  • Intestinal inflammation
  • Lymphocyte

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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