Expression of IL-27, Th1 and Th17 in patients with aplastic anemia

J Clin Immunol. 2013 Feb;33(2):436-45. doi: 10.1007/s10875-012-9810-0. Epub 2012 Sep 30.

Abstract

Background: Aplastic anemia (AA) is an autoimmune disease and interleukin-27 (IL-27) is an important cytokine involved in the pathogenesis of autoimmune diseases. To date there have been no reports concerning the intrinsic association among IL-27 and Thelper (Th) 1 and Th17 cells in AA.

Materials and methods: Enzyme-linked immunosorbent assay (ELISA) to assay IL-27, interferon gamma (IFN-γ) and IL-17 levels, flow cytometry to measure the percentages of Th1 and Th17 cells among peripheral blood mononuclear cells (PBMCs), real-time reverse transcriptase polymerase chain reaction (PCR) for the mRNA levels of IL-27, IFN-γ, T-bet and IL-17 and retinoid related orphan receptor gamma (RORγt) in PBMCs were performed. In addition, the effect of exogenous rhIL-27 on the differentiation of T cells into Th1 and Th17 cells was investigated in vitro.

Results: Plasma and mRNA levels of IL-27 in PBMCs from AA patients were significantly higher than those in healthy controls. A positive correlation was found between plasma levels of IL27 and IFN-γ. The proportions of Th1 and Th17 cells accompanied by the mRNA expression of RORγt and T-bet were significantly higher in AA patients than in healthy controls. Plasma levels of IL-27 correlated positively with frequencies of Th1 cells in AA patients. Exogenous rhIL-27 could significantly upregulate the frequency of Th1 cells and the mRNA levels of T-bet and IFN-γ and the application of rhIL-27 in vitro could inhibit the expression of RORγt mRNA.

Conclusion: The upregulation of IL-27 might cause Th1 differentiation and immune disorders in AA patients. Blocking the expression of IL-27 could therefore be a reasonable therapeutic strategy for AA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anemia, Aplastic / genetics
  • Anemia, Aplastic / immunology*
  • Anemia, Aplastic / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interleukin-17 / blood
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Interleukin-17 / pharmacology
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • RNA, Messenger / genetics
  • T-Box Domain Proteins / genetics
  • T-bet Transcription Factor
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Young Adult

Substances

  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Messenger
  • T-Box Domain Proteins
  • T-bet Transcription Factor
  • Interferon-gamma