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

Authors

  • F.-F. Ni,

    1. Shenzhen Institute of Pediatrics Affiliated Shenzhen Children's Hospital, Chongqing Medical University, Shenzhen, China
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  • C.-R. Li,

    Corresponding author
    1. Shenzhen Institute of Pediatrics Affiliated Shenzhen Children's Hospital, Chongqing Medical University, Shenzhen, China
    • Correspondences: C.-R. Li, Institute of Pediatrics, Affiliated Shenzhen Children's Hospital, Chongqing Medical University, Shenzhen 518026, China.

      E-mail: chengrongli0755@163.com

      Q. Li, Affiliated Chongqing Children's Hospital, Chongqing Medical University, Chongqing 400014, China.

      E-mail: qiuli0755@163.com

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    • These authors equally contributed to this paper.
  • Q. Li,

    Corresponding author
    1. Affiliated Chongqing Children's Hospital, Chongqing Medical University, Chongqing, China
    • Correspondences: C.-R. Li, Institute of Pediatrics, Affiliated Shenzhen Children's Hospital, Chongqing Medical University, Shenzhen 518026, China.

      E-mail: chengrongli0755@163.com

      Q. Li, Affiliated Chongqing Children's Hospital, Chongqing Medical University, Chongqing 400014, China.

      E-mail: qiuli0755@163.com

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    • These authors equally contributed to this paper.
  • Y. Xia,

    1. Shenzhen Institute of Pediatrics Affiliated Shenzhen Children's Hospital, Chongqing Medical University, Shenzhen, China
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  • G.-B. Wang,

    1. Shenzhen Institute of Pediatrics Affiliated Shenzhen Children's Hospital, Chongqing Medical University, Shenzhen, China
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  • J. Yang

    1. Shenzhen Institute of Pediatrics Affiliated Shenzhen Children's Hospital, Chongqing Medical University, Shenzhen, China
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Summary

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.

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