Increased intraepithelial Vα24 invariant NKT cells in the celiac duodenum

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 homeostasi...

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Autores principales: Montalvillo, Enrique, Bernardo, David, Martínez Abad, Beatriz, Allegretti, Yessica Lorena, Fernández Salazar, Luis, Calvo, Carmen, Chirdo, Fernando Gabriel, Garrote, José A., Arranz, Eduardo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2015
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/86366
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id I19-R120-10915-86366
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Celiac disease
Celiac disease-like molecular profile
IFNγ
INKT
Intraepithelial lymphocytes
Vα24-Jα18
spellingShingle Ciencias Exactas
Celiac disease
Celiac disease-like molecular profile
IFNγ
INKT
Intraepithelial lymphocytes
Vα24-Jα18
Montalvillo, Enrique
Bernardo, David
Martínez Abad, Beatriz
Allegretti, Yessica Lorena
Fernández Salazar, Luis
Calvo, Carmen
Chirdo, Fernando Gabriel
Garrote, José A.
Arranz, Eduardo
Increased intraepithelial Vα24 invariant NKT cells in the celiac duodenum
topic_facet Ciencias Exactas
Celiac disease
Celiac disease-like molecular profile
IFNγ
INKT
Intraepithelial lymphocytes
Vα24-Jα18
description 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 (<i>invariant</i> 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.
format Articulo
Articulo
author Montalvillo, Enrique
Bernardo, David
Martínez Abad, Beatriz
Allegretti, Yessica Lorena
Fernández Salazar, Luis
Calvo, Carmen
Chirdo, Fernando Gabriel
Garrote, José A.
Arranz, Eduardo
author_facet Montalvillo, Enrique
Bernardo, David
Martínez Abad, Beatriz
Allegretti, Yessica Lorena
Fernández Salazar, Luis
Calvo, Carmen
Chirdo, Fernando Gabriel
Garrote, José A.
Arranz, Eduardo
author_sort Montalvillo, Enrique
title Increased intraepithelial Vα24 invariant NKT cells in the celiac duodenum
title_short Increased intraepithelial Vα24 invariant NKT cells in the celiac duodenum
title_full Increased intraepithelial Vα24 invariant NKT cells in the celiac duodenum
title_fullStr Increased intraepithelial Vα24 invariant NKT cells in the celiac duodenum
title_full_unstemmed Increased intraepithelial Vα24 invariant NKT cells in the celiac duodenum
title_sort increased intraepithelial vα24 invariant nkt cells in the celiac duodenum
publishDate 2015
url http://sedici.unlp.edu.ar/handle/10915/86366
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