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

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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Figure 1: Polarization of human TH-17 cells is induced by IL-1β and IL-6 but is inhibited by TGF-β and IL-12.
Figure 2: Effects of IL-2 and IL-23 on TH-17 differentiation.
Figure 3: IL-1β and IL-6 induce RORγt expression in differentiating TH-17 cells.
Figure 4: APCs vary in their ability to secrete polarizing cytokines after activation.
Figure 5: Circulating CD14+ monocytes and CD1c+ cDCs stimulated with PGN or LPS efficiently trigger the differentiation of human IL-17-secreting T cells.
Figure 6: Monocyte-derived IL-1β and IL-6 are required for effective TH-17 polarization.

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Acknowledgements

We thank D. Jarrossay for cell sorting and discussions. Supported by the Swiss National Science Foundation (31-101962 to F.S.), the US National Institutes of Health (U19 AI057266-01) and the Helmut Horten Foundation (for The Institute for Research in Biomedicine).

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Correspondence to Eva V Acosta-Rodriguez or Federica Sallusto.

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Acosta-Rodriguez, E., Napolitani, G., Lanzavecchia, A. et al. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17–producing human T helper cells. Nat Immunol 8, 942–949 (2007). https://doi.org/10.1038/ni1496

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