Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis.
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.
Harper
Erin G
EG
Department of Dermatology, Oregon Health & Science University, Portland, Oregon 97239, USA.
Guo
Changsheng
C
Rizzo
Heather
H
Lillis
Joseph V
JV
Kurtz
Stephen E
SE
Skorcheva
Iliyana
I
Purdy
David
D
Fitch
Erin
E
Iordanov
Mihail
M
Blauvelt
Andrew
A
D000818:Animals; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000032:analysis / Q000235:genetics*; D004817:Epidermis / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000032:analysis / Q000502:physiology*; D007378:Interleukins / Q000032:analysis / Q000502:physiology; D015603:Keratinocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000209:etiology* / Q000276:immunology; D054399:Receptors, CCR6 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097043:Interleukin-22
D054418:Chemokine CCL20; D020381:Interleukin-17; D007378:Interleukins; D054399:Receptors, CCR6; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22