Interleukins 1β and 6 but Not Transforming Growth Factor-Β Are Essential for the Differentiation of Interleukin 17–producing Human T Helper Cells

Interleukin 17 (IL-17)–producing CD4 + helper T cells (T H -17 cells) have been linked to host defense and autoimmune diseases. In mice, the differentiation of T H -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 T H -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 T H -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 T H -17 cells and emphasize an important difference in the requirements for the differentiation of T H -17 cells in humans and mice.