IL-1beta and IL-2 convert human Treg into T(H)17 cells.
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.
Deknuydt
Florence
F
Institut National de la Santé et de la Recherche Médicale, Unité 892, CLCC René Gauducheau, Saint Herblain, France.
Bioley
Gilles
G
Valmori
Danila
D
Ayyoub
Maha
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D053583:Interleukin-1beta; D007376:Interleukin-2