title: Semisynthetic diet ameliorates Crohn's disease-like ileitis in TNFΔARE/WT mice through antigen-independent mechanisms of gluten.
abstract: BACKGROUND
  Enteral nutrition is used to treat a subset of patients with inflammatory bowel diseases. Because dietary factors may contribute to an aggressive immune response toward the intestinal microbiota in the disease susceptible host, we used TNFΔARE/WT mice to study the therapeutic effect of a semisynthetic experimental diet in the pathogenesis of Crohn's disease (CD)-like inflammation in the ileum.
  
  
  METHODS
  TNFΔARE/WT mice were fed chow and experimental diets partially fortified with gluten in a dose and time-dependent manner. Histopathology, markers of inflammation, intraepithelial lymphocytes phenotypes, and antigen-specific reactivation of CD4⁺ T cells were determined.
  
  
  RESULTS
  TNFΔARE/WT mice being transferred to an experimental diet with 7 but not with 10 or 14 weeks of age were protected from development of Crohn's disease-like ileitis. Although disease-related CD8αβ⁺ intraepithelial lymphocytes were increased irrespective of dietary intervention, the protective effect of experimental diet was associated with decreased expression of inflammation markers in ileal tissues. In addition, CD4⁺ T-cell reactivation in bacterial antigen-primed dendritic cell cocultures was not altered between semisynthetic and chow diet-fed TNFΔARE/WT mice, suggesting bacteria-independent mechanisms. Most importantly, gluten-fortified experimental diet induced chronic ileitis in TNFΔARE/WT mice, despite the fact that gluten-derived peptides failed to induce CD4⁺ T-cell activation. Reduced occludin expression levels suggest a negative role of gluten-fortified experimental diet on intestinal barrier integrity.
  
  
  CONCLUSIONS
  Crohn's disease-like ileitis can be prevented at early stages of disease development using a semisynthetic experimental diet. Gluten was identified as antigen-independent dietary factor relevant for the induction of chronic inflammation in the small intestine of TNFΔARE/WT mice.
authors.affiliation: ZIEL Research Center for Nutrition and Food Science, CDD Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Wagner
authors.forename: Annemarie
authors.initials: A
authors.lastname: Schmidt
authors.forename: Manuel J P
authors.initials: MJ
authors.lastname: Effenberger
authors.forename: Lisa
authors.initials: L
authors.lastname: Gruber
authors.forename: Jürgen
authors.initials: J
authors.lastname: Danier
authors.forename: Dirk
authors.initials: D
authors.lastname: Haller
mesh_terms: D000818:Animals; D000941:Antigens / Q000009:adverse effects* / Q000276:immunology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005983:Glutens / Q000009:adverse effects*; D006579:Heterozygote; D007079:Ileitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D000941:Antigens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005983:Glutens