Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17–producing human T helper cells

EV Acosta-Rodriguez, G Napolitani… - Nature …, 2007 - nature.com
Nature immunology, 2007nature.com
Abstract Interleukin 17 (IL-17)–producing CD4+ helper T cells (TH-17 cells) have been
linked to host defense and autoimmune diseases. In mice, the differentiation of TH-17 cells
requires transforming growth factor-β and IL-6 and the transcription factor RORγt. We report
here that for human naive CD4+ T cells, RORγt expression and TH-17 polarization were
induced by IL-1β and enhanced by IL-6 but were suppressed by transforming growth factor-
β and IL-12. Monocytes and conventional dendritic cells, but not monocyte-derived dendritic …
Abstract
Interleukin 17 (IL-17)–producing CD4+ helper T cells (TH-17 cells) have been linked to host defense and autoimmune diseases. In mice, the differentiation of TH-17 cells requires transforming growth factor-β and IL-6 and the transcription factor RORγt. We report here that for human naive CD4+ T cells, RORγt expression and TH-17 polarization were induced by IL-1β and enhanced by IL-6 but were suppressed by transforming growth factor-β and IL-12. Monocytes and conventional dendritic cells, but not monocyte-derived dendritic cells activated by microbial stimuli, efficiently induced TH-17 priming, and this function correlated with antigen-presenting cell production of IL-1β and IL-6 but not IL-12. Our results identify cytokines, antigen-presenting cells and microbial products that promote the polarization of human TH-17 cells and emphasize an important difference in the requirements for the differentiation of TH-17 cells in humans and mice.
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