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 journalArticle

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Abstract

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
Volume184
Issue number8
DOIs
Publication statusPublished - 2010 Apr 15

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Interleukin-23
Colitis
Macrophages
Inflammatory Bowel Diseases
Interleukin-10
Anti-Inflammatory Agents
Histone Code
Inflammation
Microbiota
Gene Expression

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Sheikh, S. Z., Matsuoka, K., Kobayashi, T., Li, F., Rubinas, T., & Plevy, S. E. (2010). Cutting edge: IFN-γ is a negative regulator of IL-23 in murine macrophages and experimental colitis. Journal of Immunology, 184(8), 4069-4073. https://doi.org/10.4049/jimmunol.0903600

Cutting edge : IFN-γ is a negative regulator of IL-23 in murine macrophages and experimental colitis. / Sheikh, Shehzad Z.; Matsuoka, Katsuyoshi; Kobayashi, Taku; Li, Fengling; Rubinas, Tara; Plevy, Scott E.

In: Journal of Immunology, Vol. 184, No. 8, 15.04.2010, p. 4069-4073.

Research output: Contribution to journalArticle

Sheikh, SZ, Matsuoka, K, Kobayashi, T, Li, F, Rubinas, T & Plevy, SE 2010, 'Cutting edge: IFN-γ is a negative regulator of IL-23 in murine macrophages and experimental colitis', Journal of Immunology, vol. 184, no. 8, pp. 4069-4073. https://doi.org/10.4049/jimmunol.0903600
Sheikh, Shehzad Z. ; Matsuoka, Katsuyoshi ; Kobayashi, Taku ; Li, Fengling ; Rubinas, Tara ; Plevy, Scott E. / Cutting edge : IFN-γ is a negative regulator of IL-23 in murine macrophages and experimental colitis. In: Journal of Immunology. 2010 ; Vol. 184, No. 8. pp. 4069-4073.
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