{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:25:27Z","timestamp":1760243127021,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,10,30]],"date-time":"2015-10-30T00:00:00Z","timestamp":1446163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI070244; PI10\/01647"],"award-info":[{"award-number":["PI070244; PI10\/01647"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014180","name":"Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["SAN673\/VA22-08","FPI-Grant (to EM)"],"award-info":[{"award-number":["SAN673\/VA22-08","FPI-Grant (to EM)"]}],"id":[{"id":"10.13039\/501100014180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Celiac Disease (CD) is an interferon (IFN)\u03b3-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. V\u03b124-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\u03b124-J\u03b118 (invariant TCR\u03b1 chain of human iNKT cells), IFN\u03b3 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\u03b124-J\u03b118 mRNA levels than non-CD controls (I and C-controls). The expression of  V\u03b124-J\u03b118 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFN\u03b3 levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of V\u03b124-J\u03b118, 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\u03b124-J\u03b118 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\u03b124-J\u03b118 together with a decreased expression of FoxP3, may represent a  pro-inflammatory signature of the CD duodenum.<\/jats:p>","DOI":"10.3390\/nu7115444","type":"journal-article","created":{"date-parts":[[2015,11,2]],"date-time":"2015-11-02T02:53:57Z","timestamp":1446432837000},"page":"8960-8976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Increased Intraepithelial V\u03b124 Invariant NKT Cells in the Celiac Duodenum"],"prefix":"10.3390","volume":"7","author":[{"given":"Enrique","family":"Montalvillo","sequence":"first","affiliation":[{"name":"Mucosal Immunology Lab, IBGM, University of Valladolid-CSIC, Sanz y For\u00e9s 3, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark\u2019s Campus, Level 7W, St Mark's Building Watford Road Harrow HA1 3UJ, UK"},{"name":"Gastroenterology Unit, Hospital Universitario de La Princesa and Instituto de Investigaci\u00f3n Sanitaria Princesa (IIS-IP), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Madrid 28006, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Mart\u00ednez-Abad","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Lab, IBGM, University of Valladolid-CSIC, Sanz y For\u00e9s 3, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yessica","family":"Allegretti","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en el Sistema Inmune \u2013LISIN, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 115, La Plata 1900, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9951-7979","authenticated-orcid":false,"given":"Luis","family":"Fern\u00e1ndez-Salazar","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Hospital Cl\u00ednico Universitario; Ram\u00f3n y Cajal 3, Valladolid 47005, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Calvo","sequence":"additional","affiliation":[{"name":"Paediatric Unit, Hospital Cl\u00ednico Universitario; Ram\u00f3n y Cajal 3, Valladolid 47005, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Chirdo","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en el Sistema Inmune \u2013LISIN, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 115, La Plata 1900, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1797-6520","authenticated-orcid":false,"given":"Jos\u00e9","family":"Garrote","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Lab, IBGM, University of Valladolid-CSIC, Sanz y For\u00e9s 3, 47003 Valladolid, Spain"},{"name":"Medical Laboratory Service, Hospital Universitario Rio Hortega; Dulzaina 2, Valladolid 47012, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Arranz","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Lab, IBGM, University of Valladolid-CSIC, Sanz y For\u00e9s 3, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1136\/gut.2010.225268","article-title":"Diversity in oat potential immunogenicity: Basis for the selection of oat varieties with no toxicity in coeliac disease","volume":"60","author":"Comino","year":"2011","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1136\/gut.2006.110361","article-title":"The pattern of cytokine expression determines the degree of mucosal damage","volume":"56","author":"Leon","year":"2007","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev-immunol-040210-092915","article-title":"Integration of genetic and immunological insights into a model of celiac disease pathogenesis","volume":"29","author":"Abadie","year":"2011","journal-title":"Annu. 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