A novel immunoregulatory function for IL-23: Inhibition of IL-12-dependent IFN-γ production

Amy N. Sieve, Karen D. Meeks, Suheung Lee, Rance E. Berg

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Most studies investigating the function of IL-23 have concluded that it promotes IL-17-secreting T cells. Although some reports have also characterized IL-23 as having redundant pro-inflammatory effects with IL-12, we have instead found that IL-23 antagonizes IL-12-induced secretion of IFN-γ.When splenocytes or purified populations of T cells were cultured with IL-23, IFN-γ secretion in response to IL-12 was dramatically reduced. The impact of IL-23 was most prominent in CD8+ T cells, but was also observed in NK and CD4+ T cells. Mechanistically, the IL-23 receptor was not required for this phenomenon, and IL-23 inhibited signaling through the IL-12 receptor by reducing IL-12-induced signal transducer and activator of transcription 4 (STAT4) phosphorylation. IL-23 was also able to reduce IFN-γ secretion by antagonizing endogenously produced IL-12 from Listeria monocytogenes (LM)-infected macrophages. In vivo, LM infection induced higher serum IFN-γ levels and a greater percentage of IFN- γ+CD8+ T cells in IL-23p19-deficient mice as compared with WT mice. This increase in IFN-γ production coincided with increased LM clearance at days 2 and 3 post-infection. Our data suggest that IL-23 may be a key factor in determining the responsiveness of lymphocytes to IL-12 and their subsequent secretion of IFN-γ.

Original languageEnglish
Pages (from-to)2236-2247
Number of pages12
JournalEuropean Journal of Immunology
Volume40
Issue number8
DOIs
StatePublished - Aug 2010

Keywords

  • CD8 T cells
  • Cytokines
  • Innate immunity
  • Listeria monocytogenes

Fingerprint Dive into the research topics of 'A novel immunoregulatory function for IL-23: Inhibition of IL-12-dependent IFN-γ production'. Together they form a unique fingerprint.

  • Cite this