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

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 RORγt, 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.