Interleukin-27 enhances the production of tumour necrosis factor-α and interferon-γ by bone marrow T lymphocytes in aplastic anaemia

Br J Haematol. 2011 Jun;153(6):764-72. doi: 10.1111/j.1365-2141.2010.08431.x. Epub 2011 Apr 21.

Abstract

Aplastic anaemia (AA) is considered as an immune-mediated bone marrow failure syndrome. The mechanism is involved with a variety of immune molecules including interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and interleukins (ILs). IL-27 is a novel member of the IL-12 family, which mediates T cell response and enhances the production of IFN-γ. However, little is known about the role of IL-27 in the development of AA. This study investigated the role of IL-27 and its receptor IL-27R in the pathogenesis of AA. Both the mRNA expression of IL-27/IL-27R subunits in the bone marrow mononuclear cells (BMMNCs) and the levels of IL-27 in the marrow plasma in AA were found to be higher than in controls. Increased IL-27 correlated with the disease severity of AA. Subsequently, we stimulated marrow T lymphocytes with recombinant human (rh)IL-27 and found that rhIL-27 enhanced the production of TNF-α and IFN-γ in both CD4(+) and CD8(+) T lymphocytes from AA patients. We also detected increased TNF-α and IFN-γ in the supernatants of BMMNCs from AA patients after IL-27 stimulation. In conclusion, our data suggest that elevated IL-27 and IL-27-induced TNF-α and IFN-γ overproduction might be involved in the pathogenesis of AA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia, Aplastic / immunology*
  • Bone Marrow Cells / immunology
  • Case-Control Studies
  • Cells, Cultured
  • Cytokine Receptor gp130 / biosynthesis
  • Cytokine Receptor gp130 / genetics
  • Female
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Male
  • Minor Histocompatibility Antigens
  • RNA, Messenger / genetics
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • EBI3 protein, human
  • IL27RA protein, human
  • IL6ST protein, human
  • Interleukin-17
  • Interleukins
  • Minor Histocompatibility Antigens
  • RNA, Messenger
  • Receptors, Interleukin
  • Tumor Necrosis Factor-alpha
  • Cytokine Receptor gp130
  • Interferon-gamma