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

Kawasaki disease (KD) is a type of systemic vasculitis syndrome related to immune dysfunction. Previous studies have implicated that dysfunctional regulatory T cells (T-reg) may be associated with the immune dysfunction in KD. In the absence of microRNAs (miRNAs), forkhead box protein 3 (FoxP3)(+) T-reg develop but fail to maintain immune homeostasis. This study was designed to investigate the effects of miR-155, miR-21 and miR-31 on T-reg in children with KD. The proportions of CD4(+)CD25(+) FoxP3(+) T-reg and the mean fluorescence intensity (MFI) of phosphorylated-signal transducer and activator of transcription (pSTAT)-5 and pSTAT-3 protein in CD4(+)CD25(+) T-reg 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(+) T-reg. The proportion of T-reg 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(+) T-reg 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.