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T300A Variant of Autophagy ATG16L1 Gene is Associated with Decreased Antigen Sampling and Processing by Dendritic Cells in Pediatric Crohn's Disease

Strisciuglio, Caterina MD*; Miele, Erasmo MD, PhD*; Wildenberg, Manon E. Dr Biol Sc, PhD; Giugliano, Francesca P. MD*; Andreozzi, Marialuisa MD*; Vitale, Alessandra Dr Biol Sc*; Capasso, Francesca PhD*; Camarca, Alessandra PhD*,‡; Barone, Maria V. MD, PhD*; Staiano, Annamaria MD*; Troncone, Riccardo MD*; Gianfrani, Carmela Dr Biol Sc*,‡

doi: 10.1097/MIB.0b013e3182a6a11c
Original Basic Science Articles

Background: The single-nucleotide polymorphism T300A of ATG16L1, a Crohn's disease (CD)–associated gene, is responsible for decreased autophagy. This study aimed to investigate the effects of this single-nucleotide polymorphism on the uptake and processing of antigens by dendritic cells (DCs) and the interaction between DC and intestinal epithelium in pediatric patients with CD.

Methods: Pediatric patients who homozygously carry either the protective (wild type, n = 7) or risk allele (risk, n = 13) of ATG16L1, as well as heterozygous patients (het, n = 13) were enrolled. The monocyte-derived DC were analyzed for phenotype, antigen sampling, and processing by flow cytometry, whereas the capability of DC to form transepithelial protrusions was determined by confocal microscopy.

Results: DC generated from wild type patients showed higher bacteria sampling and antigen processing compared with risk patients. Additionally, after exposure to either bacteria particles or the antigen DQ-ovalbumin, wild type DC showed a significant increase in the expression of the HLA-DR and CD86 when compared with risk DC. Interestingly, also het patients showed an impairment in bacteria uptake and expression of activation marker when compared with the wild type. In the Caco2/DC coculture, the formation of transepithelial protrusions were less numerous in risk DC compared with wild type and the antigen uptake decreased.

Conclusions: DC of pediatric patients with CD carrying the T300A allele showed a marked impairment of antigen uptake and processing and defective interactions between DC and intestinal epithelium. Collectively, our results suggest that an autophagy defect is associated with an impairment of intestinal innate immunity in pediatric CD.

Article first published online 9 September 2013

*Department of Pediatrics with Department of Translational Medical Science, Section of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases (E.L.F.I.D), University of Naples Federico II, Naples, Italy;

Departments of Gastroenterology and Hepatology and Tytgat Institute, Academic Medical Center, Amsterdam, the Netherlands; and

Institute of Food Sciences-CNR, Avellino, Italy.

Reprints: Riccardo Troncone, MD, Department of Pediatrics with Department of Translational Medical Science, Section of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University of Naples Federico II, Via Sergio Pansini 5, I-Naples 80131, Italy (e-mail: troncone@unina.it).

The authors have no conflicts of interest to disclose.

Received June 22, 2013

Accepted July 24, 2013

© Crohn's & Colitis Foundation of America, Inc.
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