title: Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis.
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.
authors.affiliation: Department of Dermatology, Oregon Health & Science University, Portland, Oregon 97239, USA.
authors.forename: Erin G
authors.initials: EG
authors.lastname: Harper
authors.forename: Changsheng
authors.initials: C
authors.lastname: Guo
authors.forename: Heather
authors.initials: H
authors.lastname: Rizzo
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Lillis
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kurtz
authors.forename: Iliyana
authors.initials: I
authors.lastname: Skorcheva
authors.forename: David
authors.initials: D
authors.lastname: Purdy
authors.forename: Erin
authors.initials: E
authors.lastname: Fitch
authors.forename: Mihail
authors.initials: M
authors.lastname: Iordanov
authors.forename: Andrew
authors.initials: A
authors.lastname: Blauvelt
mesh_terms: 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
chemical_list: D054418:Chemokine CCL20; D020381:Interleukin-17; D007378:Interleukins; D054399:Receptors, CCR6; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22