title: Lineage targeted MHC-II transgenic mice demonstrate the role of dendritic cells in bacterial-driven colitis.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) pathogenesis involves an inadequately controlled immune reaction to intestinal microbiota, and CD4(+) T cells, dependent on MHC class II (MHC-II) processing and presentation by antigen-presenting cells (APC), play important roles. The role of professional APC (macrophages and dendritic cells [DCs]) and nonprofessional APC (intestinal epithelial cells [IECs]) in microbial-driven intestinal inflammation remains controversial.
  
  
  METHODS
  We generated transgenic animals on an MHC-II(-/-) genetic background in which MHC-II is expressed on 1) DC via the CD11c promoter (CD11cTg) or 2) IEC via the fatty acid binding protein (liver) promoter (EpithTg). These mice were crossed with Rag2(-/-) mice to eliminate T and B cells (CD11cTg/Rag2(-/-) and EpithTg/Rag2(-/-)). Helicobacter bilis (Hb) infection and adoptive transfer (AT) of naïve CD4 T cells were used to trigger IBD.
  
  
  RESULTS
  CD11cTg/Rag2(-/-) mice infected with Hb+AT developed severe colitis within 3 weeks post-AT, similar to disease in positive control Rag2(-/-) mice infected with Hb+AT. CD11cTg/Rag2(-/-) mice given AT alone or Hb alone had significantly less severe colitis. In contrast, EpithTg/Rag2(-/-) mice infected with Hb+AT developed mild colitis by 3 weeks and even after 16 weeks post-AT had only mild lesions.
  
  
  CONCLUSIONS
  MHC-II expression restricted to DCs is sufficient to induce severe colitis in the presence of T cells and a microorganism such as Hb within 3 weeks of AT. Expression of MHC-II solely on IEC in the presence of a microbial trigger and T cells was insufficient to trigger severe colitis.
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Lillian
authors.initials: L
authors.lastname: Maggio-Price
authors.forename: Audrey
authors.initials: A
authors.lastname: Seamons
authors.forename: Helle
authors.initials: H
authors.lastname: Bielefeldt-Ohmann
authors.forename: Weiping
authors.initials: W
authors.lastname: Zeng
authors.forename: Thea
authors.initials: T
authors.lastname: Brabb
authors.forename: Carol
authors.initials: C
authors.lastname: Ware
authors.forename: Mingzu
authors.initials: M
authors.lastname: Lei
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hershberg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D039521:CD11c Antigen / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D016998:Helicobacter; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate / Q000276:immunology; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000382:microbiology
chemical_list: D039521:CD11c Antigen; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; C499308:Rag2 protein, mouse