Abstract
Natural CD4 +CD25 + regulatory T cells (Treg) and interleukin 17 (IL-17)-producing T helper cells (T H17) 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 T H17 polarizing conditions in the presence of IL-2 converts them into T H17 cells. Conversion of Tregs into T H17 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 T H17 cells from Tregs. Conversion of Treg into T H17 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 T H17 cells and establish a functional link between inflammation and autoimmunity.
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