TY - JOUR
T1 - Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo
T2 - Implications for psoriasis pathogenesis
AU - Harper, Erin G.
AU - Guo, Changsheng
AU - Rizzo, Heather
AU - Lillis, Joseph V.
AU - Kurtz, Stephen E.
AU - Skorcheva, Iliyana
AU - Purdy, David
AU - Fitch, Erin
AU - Iordanov, Mihail
AU - Blauvelt, Andrew
N1 - Funding Information:
This work was supported by a Veterans Affairs Merit Award (AB) and US National Institutes of Health Grant Nos. 1 R21 AR054495-01A1 (AB) and CA 93718 (MI).
PY - 2009/9
Y1 - 2009/9
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2009.65
DO - 10.1038/jid.2009.65
M3 - Article
C2 - 19295614
AN - SCOPUS:70349753261
SN - 0022-202X
VL - 129
SP - 2175
EP - 2183
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -