Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: Implications for psoriasis pathogenesis

Erin G. Harper, Changsheng Guo, Heather Rizzo, Joseph V. Lillis, Stephen E. Kurtz, Iliyana Skorcheva, David Purdy, Erin Fitch, Mihail Iordanov, Andrew Blauvelt

Research output: Contribution to journalArticle

266 Scopus citations

Abstract

T helper (Th) 17 cells have recently been implicated in psoriasis pathogenesis, but mechanisms of how these cells traffic into inflamed skin are unknown. By immunostaining for interleukin (IL)-17A and IL-22, we show numerous cells present in psoriasis lesions that produce these cytokines. We next found that Th17 cytokines (IL-17A, IL-22, and tumor necrosis factor (TNF)-α) markedly increased the expression of CC chemokine ligand (CCL) 20, a CC chemokine receptor (CCR)6 ligand, in human keratinocyte monolayer and raft cultures in a dose-and time-dependent manner. Lastly, we showed in mice that subcutaneous injection with recombinant IL-17A, IL-22, or TNF-α led to the upregulation of both CCL20 and CCR6 expression in skin as well as cutaneous T-cell infiltration. Taken together, these data show that Th17 cytokines stimulate CCL20 production in vitro and in vivo, and thus provide a potential explanation of how CCR6-positive Th17 cells maintain their continual presence in psoriasis through a positive chemotactic feedback loop.

Original languageEnglish (US)
Pages (from-to)2175-2183
Number of pages9
JournalJournal of Investigative Dermatology
Volume129
Issue number9
DOIs
StatePublished - Sep 1 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Harper, E. G., Guo, C., Rizzo, H., Lillis, J. V., Kurtz, S. E., Skorcheva, I., Purdy, D., Fitch, E., Iordanov, M., & Blauvelt, A. (2009). Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: Implications for psoriasis pathogenesis. Journal of Investigative Dermatology, 129(9), 2175-2183. https://doi.org/10.1038/jid.2009.65