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

Foxp3(+) Tregs 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(+) Tregs and Th17 cells plays an important role in the pathogenesis of immune-related diseases. Recent mice and human studies have demonstrated that Tregs 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 Tregs 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 Tregs 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.