title: Th17 cells carrying TCR recognizing epidermal autoantigen induce psoriasis-like skin inflammation.
abstract: Psoriasis is considered a Th17-type autoimmune skin inflammatory disease; however, involvement of an autoantigen-specific TCR has not been established. In this study, we show that psoriasis-like skin inflammation can be induced by autoreactive Th17 cells. We previously developed the desmoglein 3-specific TCR-transgenic (Dsg3H1) mouse, in which CD4⁺ T cells recognize physiological epidermal autoantigen. T cells from Dsg3H1 mice were polarized into Th17 cells in vitro and then adoptively transferred into Rag2⁻/⁻ mice. Dsg3H1-Th17 cells induced severe psoriasis-like skin inflammation within 2 wk after transfer in the tissues in which desmoglein 3 is expressed. Such pathology was not observed when wild-type Th17 cells or Th1-skewed Dsg3H1 T cells were transferred, and it was strongly suppressed by anti-IL-12/23 and anti-IL-17 Abs. Although IFN-γ⁺/IL-17⁺ T cells accumulated in the skin lesions of mice that received Dsg3H1-Th17 cells, IFN-γ-deficient Dsg3H1-Th17 cells were fully pathogenic. These results demonstrate that cutaneous psoriasis-like immunopathology can be developed by epidermis-specific recognition of Th17 cells, which is strictly dependent on IL-17 but not IFN-γ.
authors: Department of Microbiology and Immunology, Keio University School of Medicine, Shinjyuku-ku, Tokyo 160-8582, Japan.
authors: Shuhei
authors: S
authors: Nishimoto
authors: Hitoshi
authors: H
authors: Kotani
authors: Sanae
authors: S
authors: Tsuruta
authors: Nana
authors: N
authors: Shimizu
authors: Minako
authors: M
authors: Ito
authors: Takashi
authors: T
authors: Shichita
authors: Rimpei
authors: R
authors: Morita
authors: Hayato
authors: H
authors: Takahashi
authors: Masayuki
authors: M
authors: Amagai
authors: Akihiko
authors: A
authors: Yoshimura
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D002469:Cell Separation; D003872:Dermatitis / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011565:Psoriasis / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell