Interleukin-37 Inhibits the Imbalance Between T Helper 17 Cells and Regulatory T Cells in Hand, Foot, and Mouth Disease.

The aim of this study was to explore the role of interleukin-37 (IL-37) in imbalance of T helper (Th)17/regulatory T cells (Tregs) in hand, foot, and mouth disease (HFMD). The proportions of CD4+ IL-17A+ Th17 cells and CD4+ CD25+Foxp3+ Tregs in peripheral blood or peripheral blood mononuclear cells (PBMCs) from HFMD patients and healthy controls were measured by fluorescence activated cell sorter. The level of IL-37, IL-10, IL-17A, IL-23, and transforming growth factor β1 (TGF-β1) in serum or PBMCs of HFMD patients and control subjects were detected using enzyme-linked immunosorbent assay. Results showed that Th17 cells proportion and IL-17A and IL-23 levels were highly increased, whereas Tregs proportion and IL-10 and TGF-β1 levels were significantly decreased in HFMD patients. Moreover, IL-37 stimulation elevated Tregs proportion but reduced Th17 cell proportion in subjects with HFMD. On the contrary, we found methylprednisolone pulse therapy/methylprednisolone combinated with intravenous gamma globulin inhibits Th17/Treg imbalance through upregulation of IL-37 in HFMD. In conclusion, IL-37 inhibits the imbalance of Th17/Tregs in HFMD.