A role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-gamma-induced MHC class II molecule on primary human blood macrophages

J Leukoc Biol. 2010 Aug;88(2):303-11. doi: 10.1189/jlb.1009659. Epub 2010 Mar 31.


IL-10, a potent anti-inflammatory cytokine, activates its primary mediator STAT3 to exert inhibitory effects on activated immune response. It has been reported that IFN-gamma signaling can be suppressed by IL-10, which deactivates macrophages and suppresses cell-mediated antigen presentation. Cathepsin S, a cysteine protease, plays a significant role in the antigen processing. We hypothesize that the IL-10-induced and STAT3-mediated signaling pathway interferes with IFN-gamma-induced immune responses in primary human blood macrophages. Here, we investigated whether IL-10 perturbs MHC-II levels via its effect on cathepsin S expression in antigen processing. We showed that the expression of cathepsin S and MHC-II, inducible by IFN-gamma, was down-regulated in the presence of IL-10. Additionally, we revealed that the inhibitory effect of IL-10 was demonstrated to be independent of the classical IFN-gamma-induced JAK2/STAT1 signaling cascade or the NF-kappaB pathway. Following STAT3 suppression with specific siRNA, the expression of IFN-gamma-induced surface MHC-II antigens and cathepsin S levels was restored, even in the presence of IL-10. Taken together, our results demonstrated that the immunosuppressive effects of IL-10-STAT3 on MHC-II antigen presentation may occur via the inhibition of cathepsin S expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Cells
  • Cathepsins / genetics*
  • Cathepsins / physiology
  • Down-Regulation / genetics
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Immunity
  • Interferon-gamma
  • Interleukin-10 / pharmacology*
  • Macrophages / immunology*
  • STAT3 Transcription Factor / physiology*


  • Histocompatibility Antigens Class II
  • STAT3 Transcription Factor
  • Interleukin-10
  • Interferon-gamma
  • Cathepsins
  • cathepsin S