Lineage targeted MHC-II transgenic mice demonstrate the role of dendritic cells in bacterial-driven colitis

Maggio-Price, Lillian, Seamons, Audrey, Bielefeldt-Ohmann, Helle, Zeng, Weiping, Brabb, Thea, Ware, Carol, Lei, Mingzu and Hershberg, Robert M. (2013) Lineage targeted MHC-II transgenic mice demonstrate the role of dendritic cells in bacterial-driven colitis. Inflammatory Bowel Diseases, 19 1: 174-184. doi:10.1002/ibd.23000


Author Maggio-Price, Lillian
Seamons, Audrey
Bielefeldt-Ohmann, Helle
Zeng, Weiping
Brabb, Thea
Ware, Carol
Lei, Mingzu
Hershberg, Robert M.
Title Lineage targeted MHC-II transgenic mice demonstrate the role of dendritic cells in bacterial-driven colitis
Journal name Inflammatory Bowel Diseases   Check publisher's open access policy
ISSN 1078-0998
1536-4844
Publication date 2013-01
Sub-type Article (original research)
DOI 10.1002/ibd.23000
Volume 19
Issue 1
Start page 174
End page 184
Total pages 11
Place of publication United States
Publisher Lippincott Williams & Wilkins
Collection year 2014
Language eng
Formatted 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.
Keyword Dendritic cells
Intestinal epithelial cells
Adoptive transfer induced colitis
MHC II
Helicobacter bilis
Inflammatory-bowel-disease
Intestinal epithelial-cells
Cd4(+) T-cells
SCID mice
Deficient mice
In-vivo
Spontaneous proliferation
Helicobacter-hepaticus
Wasting disease
Expression
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Veterinary Science Publications
 
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