Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum

Nutrients

Enrique Montalvillo²  David Bernardo⁴  Beatriz Martínez-Abad²  Yessica Allegretti⁵  Luis Fernández-Salazar¹  Carmen Calvo³  Fernando G. Chirdo⁵  José A. Garrote² 

[1] Gastroenterology Unit, Hospital Clínico Universitario; Ramón y Cajal 3, Valladolid 47005, Spain;Mucosal Immunology Lab, IBGM, University of Valladolid-CSIC, Sanz y Forés 3, 47003 Valladolid, Spain;Paediatric Unit, Hospital Clínico Universitario; Ramón y Cajal 3, Valladolid 47005, 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;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;

关键词: Celiac Disease;    Intraepithelial Lymphocytes;    iNKT;    Vα24-Jα18;    IFNγ;    Celiac Disease-like molecular profile;   

DOI  :  10.3390/nu7115444

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.