Cutting edge: IFN-γ is a negative regulator of IL-23 in murine macrophages and experimental colitis

Shehzad Z. Sheikh, Katsuyoshi Matsuoka, Taku Kobayashi, Fengling Li, Tara Rubinas, Scott E. Plevy

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)


IL-23 regulation is a central event in the pathogenesis of the inflammatory bowel diseases. We demonstrate that IFN-γ has anti-inflammatory properties in the initiation phase of IL-23-mediated experimental colitis. IFN-γ attenuates LPS-mediated IL-23 expression in murine macrophages. Mechanistically, IFN-γ inhibits Il23a promoter activation through altering NF-κB binding and histone modification. Moreover, intestinal inflammation is inhibited by IFN-γ 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-γ. IFN-γR1/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-γ. This study describes an important anti-inflammatory role for IFN-γ through inhibition of IL-23. Converging genetic and functional findings suggest that IL-23 and IFN-γ are important pathogenic molecules in human inflammatory bowel disease.

Original languageEnglish
Pages (from-to)4069-4073
Number of pages5
JournalJournal of Immunology
Issue number8
Publication statusPublished - 2010 Apr 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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