IL-17+Foxp3+ T cells: an intermediate differentiation stage between Th17 cells and regulatory T cells

Foxp3(+) T-regs have been known as a major regulator of immune homeostasis through their immunosuppressive function. Th17 lineage is a CD4(+) T cell subset that exerts its function by secreting proinflammatory cytokines and protecting host against microbial infections. The altered ratio between Foxp3(+) T-regs and Th17 cells plays an important role in the pathogenesis of immune-related diseases. Recent mice and human studies have demonstrated that T-regs can be reprogrammed into a novel population, IL-17(+)Foxp3(+) T cells, phenotypically and functionally resembling Th17 cells under the complicated cytokine stimulation. The identification of IL-17(+)Foxp3(+) T cells may provide a new understanding of therapy targeting T-regs and Th17 cells in autoimmune diseases and cancer. Here, we highlight significant data regarding the phenotype profile, origination, differentiation, and the pleiotropic functions of IL-17(+)Foxp3(+) T cells and the reciprocal relationships of these cells to T-regs and Th17 cells. Furthermore, the role of IL-17(+)Foxp3(+) T cells in tumorigenesis and clinical implications in cancer therapy are discussed in this review.