IL-15-induced IL-10 increases the cytolytic activity of human natural killer cells

Mol Cells. 2011 Sep;32(3):265-72. doi: 10.1007/s10059-011-1057-8. Epub 2011 Jul 29.

Abstract

Interleukin 10 (IL-10) is a multifunctional cytokine that regulates diverse functions of immune cells. Natural killer (NK) cells express the IL-10 and IL-10 receptor, but little is known about the function of IL-10 on NK cell activation. In this study, we show the expression and role of IL-10 in human NK cells. Among the cytokines tested, IL-15 was the most potent inducer of IL-10, with a maximal peak expression at 5 h after treatment. Furthermore, IL-10 receptor was shown to be expressed in NK cells. IL-10 alone had a significant effect on NK cytotoxicity which additively increased NK cell cytotoxicity in the presence of IL-15. Neutralizing IL-10 with anti-IL-10 antibody suppressed the inductive effect of IL-10 on NK cell cytotoxicity; however, IL-10 had no effect on IFN-γ or TNF-α production or NK cell activatory receptor expression. STAT signals are implicated as a key mediator of IL-10/IL-15 cytotoxicity response. Thus, the effect of IL-10 on NK cells is particularly interesting with regard to the STAT3 signal that was enhanced by IL-10 or IL-15.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects
  • Cytotoxicity, Immunologic / drug effects*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-10* / antagonists & inhibitors
  • Interleukin-10* / immunology
  • Interleukin-10* / metabolism
  • Interleukin-15 / immunology*
  • Interleukin-15 / metabolism
  • Interleukin-15 / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Receptors, Interleukin-10 / immunology*
  • Receptors, Interleukin-10 / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / immunology*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies, Neutralizing
  • Interleukin-15
  • Receptors, Interleukin-10
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma