title: Regulatory T cell microRNA expression changes in children with acute Kawasaki disease.
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.
authors.affiliation: Shenzhen Institute of Pediatrics Affiliated Shenzhen Children's Hospital, Chongqing Medical University, Shenzhen, China.
authors.forename: F-F
authors.initials: FF
authors.lastname: Ni
authors.forename: C-R
authors.initials: CR
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: G-B
authors.initials: GB
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Yang
mesh_terms: D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D009080:Mucocutaneous Lymph Node Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D010641:Phenotype; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: D016756:Immunoglobulins, Intravenous; C524942:MIRN155 microRNA, human; C524940:MIRN21 microRNA, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D050826:Suppressor of Cytokine Signaling Proteins
keywords: Kawasaki disease; Treg cells; miR-155; miR-21; miR-31