CD39/CD73 and the imbalance of Th17 cells and regulatory T cells in allergic asthma

In the immune system, CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) maintain self-tolerance and Th17 cells mediate inflammatory responses. CD39 is expressed on the surface of a subset of naturally occurring human Tregs that are important in constraining pathogenic Th17 cells. Additional studies have shown that Tregs differentiate into interleukin-17 (IL-17)(+)Foxp3(+) T cells. Our previous study indicated an imbalance of Th17 and Tregs in allergic asthma; however, the underlying mechanisms remain poorly understood. Using quantitative PCR (qPCR), CD39 and CD73 mRNA levels in CD4(+) T cells were investigated. Flow cytometry was used to analyze the proportion of IL-17(+)Foxp3(+) T cells, and CD39 and CD73 expressed by CD4(+) T cells and Tregs in the peripheral blood of the subjects. The results of the present study demonstrated an increased frequency of CD4(+)Foxp3(+)IL-17(+) T cells in moderate to severe asthma. A deficiency in CD39 expressed on the surface of CD4(+) T cells and Tregs was observed in asthma patients. The expression of CD39 and CD73 on the surface of CD4(+)T cells and Tregs was negatively correlated with the number of Th17 cells. These results indicated that the plasticity of Tregs transforming to IL-17(+)Foxp3(+) CD4(+) T cells, the reduced frequency of CD39(+) Tregs and less effective suppression of IL-17 production by residual CD39(+) Tregs leads to an imbalance of Th17 and Tregs in asthma. Therefore, enhanced CD39 activity is hypothesized to prevent the progression of asthma.