title: Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesions in a mouse model.
abstract: Psoriasis is an inflammatory disease with dynamic interactions between the immune system and the skin. The IL-23/Th17 axis plays an important role in the pathogenesis of psoriasis, although the exact contributions of IL-23 and IL-17 in vivo remain unclear. K5.Stat3C transgenic mice constitutively express activated Stat3 within keratinocytes, and these animals develop skin lesions with histological and cytokine profiles similar to those of human plaque psoriasis. In this study, we characterized the effects of anti-mouse IL-17A, anti-mouse IL-12/23p40, and anti-mouse IL-23p19 Abs on the development of psoriasis-like lesions in K5.Stat3C transgenic mice. Treatment with anti-IL-12/23p40 or anti-IL-23p19 Abs greatly inhibited 12-O-tetradecanoylphorbol-13-acetate-induced epidermal hyperplasia in the ears of K5.Stat3C mice, whereas the inhibitory effect of an anti-IL-17A Ab was relatively less prominent. Treatment with anti-IL-12/23p40 or anti-IL-23p19 Abs markedly lowered transcript levels of Th17 cytokines (e.g., IL-17 and IL-22), β-defensins, and S100A family members in skin lesions. However, anti-IL-17A Ab treatment did not affect mRNA levels of Th17 cytokines. Crossing IL-17A-deficient mice with K5.Stat3C mice resulted in partial attenuation of 12-O-tetradecanoylphorbol-13-acetate-induced lesions, which were further attenuated by anti-IL-12/23p40 Ab treatment. FACS analysis of skin-draining lymph node cells from mice that were intradermally injected with IL-23 revealed an increase in both IL-22-producing T cells and NK-22 cells. Taken together, this system provides a useful mouse model for psoriasis and demonstrates distinct roles for IL-23 and IL-17.
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Okocho, Nankoku 783-8505, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Nakajima
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanda
authors.forename: Mikiro
authors.initials: M
authors.lastname: Takaishi
authors.forename: Takeo
authors.initials: T
authors.lastname: Shiga
authors.forename: Ken
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Reiko
authors.initials: R
authors.lastname: Kamijima
authors.forename: Masahito
authors.initials: M
authors.lastname: Tarutani
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Benson
authors.forename: M Merle
authors.initials: MM
authors.lastname: Elloso
authors.forename: Lester L
authors.initials: LL
authors.lastname: Gutshall
authors.forename: Michael F
authors.initials: MF
authors.lastname: Naso
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: John
authors.initials: J
authors.lastname: DiGiovanni
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sano
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000276:immunology / Q000502:physiology*; D053759:Interleukin-23 / Q000276:immunology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009418:S100 Proteins / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000633:toxicity; D023083:beta-Defensins / Q000096:biosynthesis
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D009418:S100 Proteins; D023083:beta-Defensins; D013755:Tetradecanoylphorbol Acetate