[HTML][HTML] Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis
EG Harper, C Guo, H Rizzo, JV Lillis, SE Kurtz… - Journal of Investigative …, 2009 - Elsevier
EG Harper, C Guo, H Rizzo, JV Lillis, SE Kurtz, I Skorcheva, D Purdy, E Fitch, M Iordanov…
Journal of Investigative Dermatology, 2009•ElsevierT 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 …
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 …
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.
Elsevier