Journal
JOURNAL OF IMMUNOLOGY
Volume 184, Issue 8, Pages 4069-4073Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0903600
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Funding
- National Institutes of Health [RO1 DK054452, T32 DK007737]
- National Research Service Award [F32 DK083186, P40 RR018603, P30 DK034987]
- Crohn's and Colitis Foundation of America
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IL-23 regulation is a central event in the pathogenesis of the inflammatory bowel diseases. We demonstrate that IFN-gamma has anti-inflammatory properties in the initiation phase of IL-23 mediated experimental colitis. IFN-gamma attenuates LPS-mediated IL-23 expression in murine macrophages. Mechanistically, IFN-gamma inhibits Il23a promoter activation through altering NF-kappa B binding and histone modification. Moreover, intestinal inflammation is inhibited by IFN-gamma signaling through attenuation of Il23a gene expression. In germ-free wild-type mice colonized with enteric microbiota, inhibition of colonic Il23a temporally correlates with induction of IFN-gamma R1/IL-10 double-deficient mice demonstrate markedly increased colonic inflammation and IL23a expression compared with those of IL-10(-/-) mice. Colonic CD11b(+) cells are the primary source of IL-23 and a target for IFN-gamma. This study describes an important anti-inflammatory role for IFN-gamma through inhibition of IL-23. Converging genetic and functional findings suggest that IL-23 and IFN-gamma are important pathogenic molecules in human inflammatory bowel disease. The Journal of Immunology, 2010, 184: 4069-4073.
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