CX3CL1–CX3CR1 Axis: A New Player in Coeliac Disease Pathogenesis
Marta Fernández-Prieto,
María Jesús Fernández-Aceñero,
Natalia López-Palacios,
Andrés Bodas,
Sergio Farrais,
David Cuevas,
Virginia Pascual,
M. Ángeles Cerón-Nieto,
Saúl Horta-Herrera,
Laura Espino-Paisán,
Isabel Salazar,
Concepción Núñez
Affiliations
Marta Fernández-Prieto
Laboratorio de Investigación en Genética de enfermedades complejas, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
María Jesús Fernández-Aceñero
Servicio de Anatomía Patológica, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
Natalia López-Palacios
Servicio de Aparato Digestivo, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
Andrés Bodas
Servicio de Pediatría, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
Laboratorio de Investigación en Genética de enfermedades complejas, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
Virginia Pascual
Laboratorio de Investigación en Genética de enfermedades complejas, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
M. Ángeles Cerón-Nieto
Servicio de Anatomía Patológica, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
Saúl Horta-Herrera
Laboratorio de Investigación en Genética de enfermedades complejas, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
Laura Espino-Paisán
Laboratorio de Investigación en Genética de enfermedades complejas, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
Isabel Salazar
Departamento de Producción Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain
Concepción Núñez
Laboratorio de Investigación en Genética de enfermedades complejas, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
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.