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Title: Increased intraepithelial V a 24 Invariant NKT cells in the celiac duodenum
Authors: Montalvillo Álvarez, Enrique
Bernardo, David
Martínez Abad, Beatriz
Allegretti, Yessica
Fernández Salazar, Luis Ignacio
Calvo Romero, María del Carmen
Chirdo, Fernando G.
Garrote Adrados, José Antonio
Arranz Sanz, Eduardo
Issue Date: 2015
Publisher: MDPI
Description: Producción Científica
Citation: Nutrients, vol. 7, 2015, p. 8960-8976
Abstract: 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.
Classification: Enfermedad celíaca
Biopsia duodenal
Peer Review: SI
DOI: 10.3390/nu7115444
Publisher Version:
Language: spa
Rights: info:eu-repo/semantics/openAccess
Appears in Collections:DEP55 - Artículos de revista

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