Deknuydt Florence, Bioley Gilles, Valmori Danila, Ayyoub Maha
Institut National de la Santé et de la Recherche Médicale, Unité 892, CLCC René Gauducheau, Saint Herblain, France.
Clin Immunol. 2009 May;131(2):298-307. doi: 10.1016/j.clim.2008.12.008. Epub 2009 Feb 11.
Natural CD4(+)CD25(+) regulatory T cells (Treg) and interleukin 17 (IL-17)-producing T helper cells (T(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(H)17 polarizing conditions in the presence of IL-2 converts them into T(H)17 cells. Conversion of Tregs into T(H)17 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(H)17 cells from Tregs. Conversion of Treg into T(H)17 cells was induced by IL-1beta 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(H)17 cells and establish a functional link between inflammation and autoimmunity.
天然CD4(+)CD25(+)调节性T细胞（Treg）和产生白细胞介素17（IL-17）的辅助性T细胞（Th17）发挥相反的功能，前者维持自身耐受性，后者参与炎症和自身免疫。我们在此报告，在IL-2存在的情况下，在Th17极化条件下刺激人天然Treg会将它们转化为Th17细胞。Treg向Th17细胞的转化既发生于天然初始Treg（NnTreg），也更大量地发生于记忆Treg（MTreg）。在抗原呈递细胞中，经微生物刺激激活的新鲜单核细胞是将Treg诱导为Th17细胞的最有效诱导剂。Treg向Th17细胞的转化由IL-1β诱导，涉及Treg谱系转录因子FOXP3的下调和抑制功能。我们的结果表明，在炎症条件下，在IL-2存在时，Treg可转化为促炎性Th17细胞，并在炎症和自身免疫之间建立功能联系。
