Regulatory T cell microRNA expression changes in children with acute Kawasaki disease

Clin Exp Immunol. 2014 Nov;178(2):384-93. doi: 10.1111/cei.12418.

Abstract

Kawasaki disease (KD) is a type of systemic vasculitis syndrome related to immune dysfunction. Previous studies have implicated that dysfunctional regulatory T cells (Treg ) may be associated with the immune dysfunction in KD. In the absence of microRNAs (miRNAs), forkhead box protein 3 (FoxP3)(+) Treg develop but fail to maintain immune homeostasis. This study was designed to investigate the effects of miR-155, miR-21 and miR-31 on Treg in children with KD. The proportions of CD4(+) CD25(+) FoxP3(+) Treg and the mean fluorescence intensity (MFI) of phosphorylated-signal transducer and activator of transcription (pSTAT)-5 and pSTAT-3 protein in CD4(+) CD25(+) Treg were analysed by flow cytometry. The concentration of interleukin (IL)-6 in plasma was measured by cytometric bead array. Real-time polymerase chain reaction was performed to detect the levels of microRNAs and associated factors in CD4(+) CD25(+) Treg . The proportion of Treg and the mRNA levels of the associated factors [FoxP3, glucocorticoid-induced tumour necrosis factor-receptor (GITR), cytotoxic T lymphocyte antigen (CTLA)-4)] were significantly lower in KD patients (P < 0·05). MiR-155 and miR-21 levels were significantly down-regulated and miR-31 expression was higher in KD patients (P < 0·05). Plasma interleukin (IL)-6 concentrations, pSTAT-3 protein levels and suppressors of cytokine signalling (SOCS)-1 mRNA expression were remarkably elevated in acute KD (P < 0·05), while pSTAT-5 protein levels were remarkably decreased in acute KD (P < 0·05). These findings were reversed after intravenous immunoglobulin treatment (P < 0·05). Our results demonstrate that FoxP3 mRNA levels were primarily affected by the miR-155/SOCS1 and the miR-31 signalling pathways. These results suggest that the decrease in FoxP3(+) Treg might be associated with decreased expression of miR-155, leading to aberrant SOCS1/STAT-5 signalling and overexpression of miR-31 in patients with acute KD.

Keywords: Kawasaki disease; Treg cells; miR-155; miR-21; miR-31.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunophenotyping
  • Infant
  • Male
  • MicroRNAs / genetics*
  • Models, Biological
  • Mucocutaneous Lymph Node Syndrome / diagnosis
  • Mucocutaneous Lymph Node Syndrome / genetics*
  • Mucocutaneous Lymph Node Syndrome / immunology
  • Mucocutaneous Lymph Node Syndrome / therapy
  • Phenotype
  • Signal Transduction
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Immunoglobulins, Intravenous
  • MIRN155 microRNA, human
  • MIRN21 microRNA, human
  • MIRN31 microRNA, human
  • MicroRNAs
  • Suppressor of Cytokine Signaling Proteins