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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Acknowledgements

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

Author information

Author notes

    • Jason R Chan

    Present address: Entelos, Foster City, California 94404, USA.

Affiliations

  1. Department of Discovery Research, Schering-Plough Biopharma (formerly DNAX Research), Palo Alto, California 94304-1104, USA.

    • Nicholas J Wilson
    • , Katia Boniface
    • , Jason R Chan
    • , Brent S McKenzie
    • , Robert A Kastelein
    • , Daniel J Cua
    • , Edward P Bowman
    •  & Rene de Waal Malefyt
  2. Department of Experimental Pathology and Pharmacology, Schering-Plough Biopharma (formerly DNAX Research), Palo Alto, California 94304-1104, USA.

    • Wendy M Blumenschein
    • , Jeanine D Mattson
    • , Beth Basham
    • , Kathleen Smith
    • , Taiying Chen
    •  & Terrill K McClanahan
  3. Laboratoire Cytokines et Inflammation EA 3806, Universite de Poitiers, Centre Hospitalier Universitaire de Poitiers, Pole Biologie Sante, Pineau, 86022 Poitiers, France.

    • Franck Morel
    •  & Jean-Claude Lecron

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Competing interests

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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Correspondence to Rene de Waal Malefyt.

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https://doi.org/10.1038/ni1497

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