Defective expression of scavenger receptors in celiac disease mucosa.

Maria Laura Cupi,Giovanna Del Vecchio Blanco,Daniela De Nitto,Giovanni Monteleone,Alfredo Colantoni,Massimiliano Sarra,Francesco Pallone,Irene Marafini,Ivan Monteleone,Davide Di Fusco,Angela Ortenzi,Eleonora Franzè,Omero Alessandro Paoluzi,Paolo Gentileschi,Joseph El Khoury

doi:10.1371/journal.pone.0100980

Maria Laura Cupi, Giovanna Del Vecchio Blanco + Show 13 more

Open Access

https://doi.org/10.1371/journal.pone.0100980

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Journal: PloS one	Publication Date: Jun 27, 2014
Citations: 8	License type: CC BY 4.0

Affiliation: University of Rome Tor Vergata

Abstract

Celiac disease (CD) is a gluten sensitive enteropathy characterized by a marked infiltration of the mucosa with immune cells, over-production of inflammatory cytokines and epithelial cell damage. The factors/mechanisms that sustain and amplify the ongoing mucosal inflammation in CD are not however fully understood. Here, we have examined whether in CD there is a defective clearance of apoptotic cells/bodies, a phenomenon that helps promote tolerogenic signals thus liming pathogenic responses. Accumulation of apoptotic cells and bodies was more pronounced in the epithelial and lamina propria compartments of active CD patients as compared to inactive CD patients and normal controls. Expression of scavenger receptors, which are involved in the clearance of apoptotic cells/bodies, namely thrombospondin (TSP)-1, CD36 and CD61, was significantly reduced in active CD as compared to inactive CD and normal mucosal samples. Consistently, lamina propria mononuclear cells (LPMC) of active CD patients had diminished ability to phagocyte apoptotic cells. Interleukin (IL)-15, IL-21 and interferon-γ, cytokines over-produced in active CD, inhibited the expression of TSP-1, CD36, and CD61 in normal intestinal LPMC. These results indicate that CD-related inflammation is marked by diminished clearance of apoptotic cells/bodies, thus suggesting a role for such a defect in the ongoing mucosal inflammation in this disorder.

Highlights

Celiac disease (CD) is a chronic enteropathy that occurs in genetically-predisposed individuals following ingestion of gluten proteins of wheat, rye, and barley
RNA expression of TSP-1 and CD61 was significantly reduced in ACD samples as compared to non-CD controls (NC) and inactive CD (ICD), while there was no significant difference between ICD and NC (Fig. 2A–C)
The findings of the present study demonstrate that the active phases of CD are characterized by accumulation of apoptotic cells/bodies in the duodenal mucosa, confirming data of previous studies [11,12,13], and diminished expression of macrophage-associated scavenger receptors, which are important in the recognition of exposed phosphatidylserine on the surface of apoptotic cells

Summary

Introduction

Celiac disease (CD) is a chronic enteropathy that occurs in genetically-predisposed individuals following ingestion of gluten proteins of wheat, rye, and barley. It has been demonstrated that gluten peptides can activate both innate and adaptive immune cells with the downstream effect of producing a vast array of inflammatory cytokines [3,4]. One such cytokine is interleukin (IL)-15, which activates antigen-non specific CD8+ T cells and NK cells and facilitates epithelial cell damage [5]. There is evidence that CD-related inflammation is marked by increased apoptosis of immune cells and enterocytes, suggesting that mucosal flattening is a consequence of exaggerated epithelial cell death [11,12,13]

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