Human monocytes have increased IFN-γ-mediated IL-15 production with age alongside altered IFN-γ receptor signaling

Clin Immunol. 2014 May-Jun;152(1-2):101-10. doi: 10.1016/j.clim.2014.03.003. Epub 2014 Mar 19.

Abstract

IL-15 is involved in regulating host defense and inflammation. Monocytes produce the biologically active cell surface IL-15 in response to IFN-γ. Although aging can alter the immune system, little is known about whether and how aging affects IFN-γ-mediated IL-15 production in human monocytes. We showed that monocytes of healthy older adults (age ≥ 65) had increased cell surface IL-15 expression in response to IFN-γ compared to those of healthy young adults (age ≤ 40). This finding stems in part from increased IFN-γ receptor (R)1/2 expression on monocytes in older adults, leading to enhanced STAT1 activation and interferon regulatory factor 1 synthesis with increased IL15 gene expression. Our study suggests that with aging the IFN-γ-mediated IL-15 production pathway in human monocytes is uncompromised, but rather augmented, and could be considered as a therapeutic target point to modulate host defense and inflammation in older adults.

Keywords: Human; IFN-γ; IL-15; Monocytes and aging.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Aging / immunology
  • Humans
  • Inflammation / immunology
  • Interferon Regulatory Factor-1 / biosynthesis
  • Interferon gamma Receptor
  • Interferon-gamma / metabolism*
  • Interleukin-15 / biosynthesis
  • Interleukin-15 / immunology
  • Interleukin-15 / metabolism*
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Receptors, Interferon / biosynthesis
  • Receptors, Interferon / immunology
  • Receptors, Interferon / metabolism*
  • Receptors, Interleukin-15 / immunology
  • Receptors, Interleukin-15 / metabolism
  • STAT1 Transcription Factor / immunology
  • Signal Transduction / immunology

Substances

  • IL15RA protein, human
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Interleukin-15
  • Receptors, Interferon
  • Receptors, Interleukin-15
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Interferon-gamma