caa a22 4500 445794437 CHVBK 20180317145120.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s10620-010-1534-5 doi (NATIONALLICENCE)springer-10.1007/s10620-010-1534-5 Dynamics of Non-conventional Intraepithelial Lymphocytes—NK, NKT, and γδ T—in Celiac Disease: Relationship with Age, Diet, and Histopathology [Elektronische Daten] [Sara Calleja, Santiago Vivas, María Santiuste, Laura Arias, Mercedes Hernando, Esther Nistal, Javier Casqueiro, Jose Ruiz de Morales] Background: Intraepithelial lymphocytes (IEL) are a heterogeneous population of lymphocytes raised in celiac disease (CD), whose role in CD pathogenesis remains to be defined. Aims: To investigate how the age of diagnosis, diet, and the severity of the histological lesions are related to the changes observed in unconventional IEL populations. Methods: Prospective analysis of 101 confirmed celiac patients from a single center, including 66 at diagnosis (45 children, 21 adults) and 112 non-celiac controls (12 children, 100 adults). IEL from duodenal biopsies were studied by six-color flow cytometry. The results were analyzed in relationship with age, diet (gluten intake), and histopathology (Marsh type). Results: In comparison with respective age controls, both children and adult patients showed duodenal intraepithelial lymphocytosis with significant differences in every single non-conventional IEL population: CD3+ TCR γδ, NK (CD3−, CD16+, CD56+), NKT (CD3+, CD161+, CD56+), and iNKT (CD3+ Vα24) (P<0.001 for all). Gluten intake was not only directly associated with severe atrophy, but also with decreased percentages of NK (P=0.02), NKT (P=0.003), and iNKT (P=0.03). Changes in iNKT and γδ IEL were more marked in celiac children compared with celiac adults (P=0.02 and 0.01, respectively). In contrast, increased CD3+ TCR γδ were diet- and Marsh grade-independent. Conclusions: The typical phenotypical profile of intraepithelial lymphocytosis in untreated pediatric and adult celiacs consists of increased CD3+ TCR γδ populations with decreased NK, NKT, and iNKT cells. NK, NKT, and iNKT IEL, but not γδ IEL, are dynamic populations associated with diet, age, and histopathology. Springer Science+Business Media, LLC, 2011 Celiac disease nationallicence Intraepithelial lymphocytes nationallicence Flow cytometry nationallicence γδ lymphocytes nationallicence NK lymphocytes nationallicence NKT lymphocytes nationallicence Calleja Sara Department of Immunology, Complejo Hospitalario Universitario de León, Altos de Nava s/n, 24080, León, Spain aut Vivas Santiago Department of Gastroenterology, Complejo Hospitalario Universitario de León, León, Spain aut Santiuste María Department of Immunology, Complejo Hospitalario Universitario de León, Altos de Nava s/n, 24080, León, Spain aut Arias Laura Department of Gastroenterology, Complejo Hospitalario Universitario de León, León, Spain aut Hernando Mercedes Department of Pathology, Complejo Hospitalario Universitario de León, León, Spain aut Nistal Esther Area of Microbiology, Faculty of Biology and Environmental Sciences, University of León, León, Spain aut Casqueiro Javier Area of Microbiology, Faculty of Biology and Environmental Sciences, University of León, León, Spain aut Ruiz de Morales Jose Department of Immunology, Complejo Hospitalario Universitario de León, Altos de Nava s/n, 24080, León, Spain aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/7(2011-07-01), 2042-2049 0163-2116 56:7<2042 2011 56 10620 https://doi.org/10.1007/s10620-010-1534-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1534-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Calleja Sara Department of Immunology, Complejo Hospitalario Universitario de León, Altos de Nava s/n, 24080, León, Spain aut NATIONALLICENCE 700 1- Vivas Santiago Department of Gastroenterology, Complejo Hospitalario Universitario de León, León, Spain aut NATIONALLICENCE 700 1- Santiuste María Department of Immunology, Complejo Hospitalario Universitario de León, Altos de Nava s/n, 24080, León, Spain aut NATIONALLICENCE 700 1- Arias Laura Department of Gastroenterology, Complejo Hospitalario Universitario de León, León, Spain aut NATIONALLICENCE 700 1- Hernando Mercedes Department of Pathology, Complejo Hospitalario Universitario de León, León, Spain aut NATIONALLICENCE 700 1- Nistal Esther Area of Microbiology, Faculty of Biology and Environmental Sciences, University of León, León, Spain aut NATIONALLICENCE 700 1- Casqueiro Javier Area of Microbiology, Faculty of Biology and Environmental Sciences, University of León, León, Spain aut NATIONALLICENCE 700 1- Ruiz de Morales Jose Department of Immunology, Complejo Hospitalario Universitario de León, Altos de Nava s/n, 24080, León, Spain aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/7(2011-07-01), 2042-2049 0163-2116 56:7<2042 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer