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

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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. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.

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Maggio-Price, L., Seamons, A., Bielefeldt-Ohmann, H., Zeng, W., Brabb, T., Ware, C., … Hershberg, R. 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. https://doi.org/10.1002/ibd.23000

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