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

J Invest Dermatol. 2009 Sep;129(9):2175-83. doi: 10.1038/jid.2009.65. Epub 2009 Mar 19.

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)-alpha) 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-alpha 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokine CCL20 / analysis
  • Chemokine CCL20 / genetics*
  • Epidermis / immunology
  • Humans
  • Interleukin-17 / analysis
  • Interleukin-17 / physiology*
  • Interleukins / analysis
  • Interleukins / physiology
  • Keratinocytes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Psoriasis / etiology*
  • Psoriasis / immunology
  • Receptors, CCR6 / genetics
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Chemokine CCL20
  • Interleukin-17
  • Interleukins
  • Receptors, CCR6
  • Tumor Necrosis Factor-alpha
  • interleukin-22