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¹ Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892
² Immunology and Infection Unit, Department of Biology, University of York and The Hull York Medical School, York YO10 5YW, UK
³ Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
⁴ Animal Health Diagnostic Laboratory, Laboratory Animal Sciences Program, National Cancer Institute-FCRDC, Science Applications International Corporation, Frederick, MD 21702
⁵ Department of Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304
⁶ The Biomedical Research Institute, Rockville, MD 20852

CORRESPONDENCE Marika C. Kullberg: mk512{at}york.ac.uk

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is caused in part by a dysregulated immune response to the intestinal flora. The common interleukin (IL)-12/IL-23p40 subunit is thought to be critical for the pathogenesis of IBD. We have analyzed the role of IL-12 versus IL-23 in two models of Helicobacter hepaticus–triggered T cell–dependent colitis, one involving anti–IL-10R monoclonal antibody treatment of infected T cell–sufficient hosts, and the other involving CD4⁺ T cell transfer into infected Rag^–/– recipients. Our data demonstrate that IL-23 and not IL-12 is essential for the development of maximal intestinal disease. Although IL-23 has been implicated in the differentiation of IL-17–producing CD4⁺ T cells that alone are sufficient to induce autoimmune tissue reactivity, our results instead support a model in which IL-23 drives both interferon and IL-17 responses that together synergize to trigger severe intestinal inflammation.

K.J. Maloy and A. Sher contributed equally to this work.

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J. Exp. Med. 2006 203: 2473-2483. [Abstract] [Full Text] [PDF]

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