title: T300A variant of autophagy ATG16L1 gene is associated with decreased antigen sampling and processing by dendritic cells in pediatric Crohn's disease.
abstract: 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.
authors.affiliation: *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.
authors.forename: Caterina
authors.initials: C
authors.lastname: Strisciuglio
authors.forename: Erasmo
authors.initials: E
authors.lastname: Miele
authors.forename: Manon E
authors.initials: ME
authors.lastname: Wildenberg
authors.forename: Francesca P
authors.initials: FP
authors.lastname: Giugliano
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Andreozzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vitale
authors.forename: Francesca
authors.initials: F
authors.lastname: Capasso
authors.forename: Alessandra
authors.initials: A
authors.lastname: Camarca
authors.forename: Maria V
authors.initials: MV
authors.lastname: Barone
authors.forename: Annamaria
authors.initials: A
authors.lastname: Staiano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Troncone
authors.forename: Carmela
authors.initials: C
authors.lastname: Gianfrani
mesh_terms: D000293:Adolescent; D000328:Adult; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D055815:Young Adult
chemical_list: C518959:ATG16L1 protein, human; D000942:Antigens, Bacterial; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins