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-beta and IL-6 and the transcription factor ROR gamma t. We report here that for human naive CD4+ T cells, ROR gamma t expression and T-H-17 polarization were induced by IL-1 beta and enhanced by IL-6 but were suppressed by transforming growth factor-beta 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-1b 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.