IL-17A-Producing Foxp3(+) Regulatory T Cells and Human Diseases

Abstract

CD4(+)Foxp3(+) regulatory T (Treg) cells play major roles in immune homeostasis. While CD4(+)Foxp3(+) Treg cells act to suppress other immune effector cells, there is growing evidence that they also produce pro-inflammatory cytokines, such as IL-17A, in inflammatory conditions. The pro-inflammatory cytokine milieu, toll-like receptor (TLR) signaling, and specific transcription factors are important for the production of IL-17A by CD4(+)Foxp3(+) Treg cells. In particular, IL-17A-producing CD4(+)Foxp3(+) Treg cells express ROR gamma t, the T helper (Th) 17-specific transcription factor, in addition to Foxp3. IL-17A-producing CD4(+)Foxp3(+) Treg cells are also involved in the pathogenesis of various diseases. Here we review the mechanisms underlying the induction of IL-17A-producing CD4(+)Foxp3(+) Treg cells and the roles of these cells in human disease.