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Development, cytokine profile and function of human interleukin 17–producing helper T cells

Abstract

TH-17 cells are a distinct lineage of proinflammatory T helper cells that are essential for autoimmune disease. In mice, commitment to the TH-17 lineage is dependent on transforming growth factor-β and interleukin 6 (IL-6). Here we demonstrate that IL-23 and IL-1β induced the development of human TH-17 cells expressing IL-17A, IL-17F, IL-22, IL-26, interferon-γ, the chemokine CCL20 and transcription factor RORγt. In situ, TH-17 cells were identified by expression of the IL-23 receptor and the memory T cell marker CD45RO. Psoriatic skin lesions contained IL-23-producing dendritic cells and were enriched in the cytokines produced by human TH-17 cells that promote the production of antimicrobial peptides in human keratinocytes. Our data collectively indicate that human and mouse TH-17 cells require distinct factors during differentiation and that human TH-17 cells may regulate innate immunity in epithelial cells.

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Figure 1: IL-23, but not a combination of TGF-β and IL-6, promotes the development of TH-17 cells from human naive CD4+ T cells.
Figure 2: IL-23 and IL-1β drive the differentiation of human TH-17 cells.
Figure 3: Human memory CD4+ T cells express IL-23R, produce substantial amounts of IL-17A and express the same set of cytokines as in vitro–polarized TH-17 cells.
Figure 4: IL-23p19 and TH-17 effector cytokines are associated with human psoriasis.
Figure 5: TH-17 effector cytokines elicit the expression of antimicrobial molecules from human keratinocytes.

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Acknowledgements

Supported by the National Health and Medical Research Council of Australia (N.J.W.).

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Correspondence to Rene de Waal Malefyt.

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N.J.W., K.B., J.R.C., B.S.M., W.M.B., J.D.M., B.B., K.S., T.C., R.A.K., D.J.C., T.K.M., E.P.B. & R.d.W.M. are employed by Schering-Plough Biopharma, which is supported by Schering-Plough Corporation.

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Wilson, N., Boniface, K., Chan, J. et al. Development, cytokine profile and function of human interleukin 17–producing helper T cells. Nat Immunol 8, 950–957 (2007). https://doi.org/10.1038/ni1497

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