The T helper type 17/regulatory T cell imbalance in patients with acute Kawasaki disease

Abstract

The study is designed to investigate the changes and roles of T helper type 17/regulatory T cells (Th17/T_reg) in the immunological pathogenesis of Kawasaki disease (KD). In addition, we explore the alteration and significance of Th17 cells in patients with intravenous immune globulin-resistant KD. Real-time polymerase chain reaction (PCR) was used to evaluate the mRNA levels of interleukin (IL)-17A/F, retinoic acid-related orphan receptor (ROR)-γt and forkhead box P3 (FoxP3) in CD4-positive cells. The proportions of Th17 cells and CD4⁺CD25⁺FoxP3^high T_regs were analysed by flow cytometry. Plasma cytokine [IL-17A, IL-6, IL-23 and transforming growth factor (TGF)-β] concentrations were measured by sandwich enzyme-linked immunosorbent assay. Our data demonstrate that Th17 proportions and expression levels of cytokines (IL-17, IL-6 and IL-23) and transcription factors (IL-17A/F, ROR-γt) were up-regulated significantly, while T_reg proportions and expression levels of T_reg transcription factor (FoxP3) were down-regulated significantly in children with acute KD (P < 0·01). Compared with the sensitive group, the Th17 proportions were up-regulated significantly during the acute phase in immune globulin-resistant KD (P < 0·01). The plasma IL-17A, IL-6 and IL-23 concentrations in patients with KD were significantly higher compared with the concentrations in normal controls (NC) and infectious disease (ID). Plasma TGF-β concentrations were markedly lower in the KD group than the NC and ID groups (P < 0·05). These results suggest that Th17/T_reg cells imbalance exists in the patients with KD. Th17/T cells imbalance may be important factors causing disturbed immunological function and resulting in immunoglobulin-resistant KD.