Published online 9 October 2006 doi:10.1084/jem.20061099
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 11, 2473-2483
Interleukin-23 drives innate and T cellmediated intestinal inflammation
Sophie Hue1,
Philip Ahern1,
Sofia Buonocore1,
Marika C. Kullberg2,
Daniel J. Cua3,
Brent S. McKenzie3,
Fiona Powrie1, and
Kevin J. Maloy1
1 Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, England, UK
2 Immunology and Infection Unit, Department of Biology, University of York and The Hull York Medical School, York YO10 5YW, England, UK
3 Department of Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304
CORRESPONDENCE Kevin Maloy: kevin.maloy{at}path.ox.ac.uk OR Fiona Powrie: fiona.powrie{at}path.ox.ac.uk
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract involving aberrant activation of innate and adaptive immune responses. We have used two complementary models of IBD to examine the roles of interleukin (IL)-12 family cytokines in bacterially induced intestinal inflammation. Our results clearly show that IL-23, but not IL-12, is essential for the induction of chronic intestinal inflammation mediated by innate or adaptive immune mechanisms. Depletion of IL-23 was associated with decreased proinflammatory responses in the intestine but had little impact on systemic T cell inflammatory responses. These results newly identify IL-23 as a driver of innate immune pathology in the intestine and suggest that selective targeting of IL-23 represents an attractive therapeutic approach in human IBD.
Abbreviations used: CD, Crohn's disease; IBD, inflammatory bowel disease; FSC, forward scatter; KC, mouse chemokine CXCL1; LPL, lamina propria leukocyte; MCP-1, monocyte chemoattractant protein1; MLN, mesenteric LN; Q-PCR, quantitative PCR; SSC, side scatter.

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