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Increased Intraepithelial V?24 Invariant NKT Cells in the Celiac Duodenum.


ABSTRACT: Celiac Disease (CD) is an interferon (IFN)?-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. V?24-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 V?24-J?18 (invariant TCR? chain of human iNKT cells), IFN? 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 V?24-J?18 mRNA levels than non-CD controls (I and C-controls). The expression of V?24-J?18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFN? levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of V?24-J?18, 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 V?24-J?18 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 V?24-J?18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum.

SUBMITTER: Montalvillo E 

PROVIDER: S-EPMC4663572 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

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