IL-1β and IL-2 convert human Treg into TH17 cells

Natural CD4+CD25+ regulatory T cells (Treg) and interleukin 17 (IL-17)-producing T helper cells (TH17) carry out opposite functions, the former maintaining self-tolerance and the latter being involved in inflammation and autoimmunity. We report here that stimulation of human Natural Treg under TH17 polarizing conditions in the presence of IL-2 converts them into TH17 cells. Conversion of Tregs into TH17 cells occurs both from natural naïve Tregs (NnTregs) and, to a higher extent, from memory Tregs (MTregs). Among antigen presenting cells, fresh monocytes activated by microbial stimuli were the most efficient inducers of TH17 cells from Tregs. Conversion of Treg into TH17 cells was induced by IL-1β and involved down-regulation of the Treg lineage transcription factor FOXP3 and suppressive functions. Our results indicate that, under inflammatory conditions, in the presence of IL-2, Treg can be converted into pro-inflammatory TH17 cells and establish a functional link between inflammation and autoimmunity.