IL-1 beta and IL-2 convert human Treg into T sub(H)17 cells

• Published in: Clinical immunology (Orlando, Fla.) Vol. 131; no. 2; pp. 298 - 307
• Main Authors: Deknuydt, F, Bioley, G, Valmori, D, Ayyoub, M
• Format: Journal Article
• Language: English
• Published: 01.05.2009
• ISSN: 1521-6616
• DOI: 10.1016/j.clim.2008.12.008

Natural CD4 super(+)CD25 super(+) regulatory T cells (Treg) and interleukin 17 (IL-17)-producing T helper cells (T sub(H)17) 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 sub(H)17 polarizing conditions in the presence of IL-2 converts them into T sub(H)17 cells. Conversion of Tregs into T sub(H)17 cells occurs both from natural naive 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 sub(H)17 cells from Tregs. Conversion of Treg into T sub(H)17 cells was induced by IL-1 beta 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 sub(H)17 cells and establish a functional link between inflammation and autoimmunity.