CX3CL1-CX3CR1 Axis: A New Player in Coeliac Disease Pathogenesis.

Marta Fernández-Prieto,Laura Espino-Paisán,Virginia Pascual,Concepción Núñez,María Jesús Fernández-Aceñero,Natalia López-Palacios,Isabel Salazar,David Cuevas,Sergio Farrais,Saúl Horta-Herrera,Andrés Bodas,M Ángeles Cerón-Nieto

doi:10.3390/nu11112551

Abstract

Background: The CX3CL1–CX3CR1 axis has been related to numerous diseases. The aim of our study was to investigate its involvement in coeliac disease (CD) pathogenesis, particularly in the early phase of the disease. Methods: We collected peripheral blood from CD patients and controls, enrolled in a 3-day gluten challenge, to study soluble CX3CL1, I-TAC and MIG by Luminex, CX3CL1 and CX3CR1 gene expression by qPCR, and CX3CR1 protein expression in monocytes and CD8+, CD4+ and γδ+ T cells, by flow cytometry. We also analysed the expression of the CX3CL1 and CX3CR1 mRNA and protein in the duodenal biopsies of CD patients with active and treated disease, and in non-CD control individuals, by qPCR and immunohistochemistry. Results: After the gluten challenge, increased levels of CX3CL1, I-TAC and MIG proteins were observed in the peripheral blood of CD patients, with no changes in CX3CL1 mRNA, or CX3CR1 mRNA and protein. Regarding duodenal tissue, CX3CL1 was absent or barely present in the superficial and basal epithelium of CD patients, contrasting with the moderate to high levels present in controls. Conclusions: CX3CL1 seems to be involved in the appearance and progression of CD, and it appears to be a potential diagnostic biomarker. Its use as an alternative therapeutic target in CD deserves further research.

Highlights

Chemokines have been widely related to autoimmunity and inflammation, due to their key role in the selective recruitment of leukocytes
We demonstrated an increase of IFN-γ and IP-10 in the peripheral blood of coeliac disease (CD) patients six days after starting such a gluten challenge protocol
We aim to investigate the role of the CX3CL1–CX3CR1 axis in CD, as well as its potential involvement, together with CXCR3 ligands, as diagnostic markers in the first steps after a gluten challenge

Summary

Introduction

Chemokines have been widely related to autoimmunity and inflammation, due to their key role in the selective recruitment of leukocytes. Methods: We collected peripheral blood from CD patients and controls, enrolled in a 3-day gluten challenge, to study soluble CX3CL1, I-TAC and MIG by Luminex, CX3CL1 and CX3CR1 gene expression by qPCR, and CX3CR1 protein expression in monocytes and CD8+ , CD4+ and γδ+ T cells, by flow cytometry. MRNA and protein in the duodenal biopsies of CD patients with active and treated disease, and in non-CD control individuals, by qPCR and immunohistochemistry. Results: After the gluten challenge, increased levels of CX3CL1, I-TAC and MIG proteins were observed in the peripheral blood of CD patients, with no changes in CX3CL1 mRNA, or CX3CR1 mRNA and protein. CX3CL1 was absent or barely present in the superficial and basal epithelium of CD patients, contrasting with the moderate to high levels present in controls. Its use as an alternative therapeutic target in CD deserves further research

Objectives

Methods

Conclusion