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Nutrients 2015, 7(11), 8960-8976;

Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum

Mucosal Immunology Lab, IBGM, University of Valladolid-CSIC, Sanz y Forés 3, 47003 Valladolid, Spain
Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark’s Campus, Level 7W, St Mark's Building Watford Road Harrow HA1 3UJ, UK
Gastroenterology Unit, Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid 28006, Spain
Laboratorio de Investigación en el Sistema Inmune –LISIN, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 115, La Plata 1900, Buenos Aires, Argentina
Gastroenterology Unit, Hospital Clínico Universitario; Ramón y Cajal 3, Valladolid 47005, Spain
Paediatric Unit, Hospital Clínico Universitario; Ramón y Cajal 3, Valladolid 47005, Spain
Medical Laboratory Service, Hospital Universitario Rio Hortega; Dulzaina 2, Valladolid 47012, Spain
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 23 July 2015 / Revised: 16 October 2015 / Accepted: 21 October 2015 / Published: 30 October 2015
(This article belongs to the Special Issue Gluten Related Disorders: People Shall not Live on Bread Alone)
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Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum. View Full-Text
Keywords: Celiac Disease; Intraepithelial Lymphocytes; iNKT; Vα24-Jα18; IFNγ; Celiac Disease-like molecular profile Celiac Disease; Intraepithelial Lymphocytes; iNKT; Vα24-Jα18; IFNγ; Celiac Disease-like molecular profile

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Montalvillo, E.; Bernardo, D.; Martínez-Abad, B.; Allegretti, Y.; Fernández-Salazar, L.; Calvo, C.; Chirdo, F.G.; Garrote, J.A.; Arranz, E. Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum. Nutrients 2015, 7, 8960-8976.

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