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 | Shuhei Nishimoto, Hitoshi Kotani, Sanae Tsuruta, Nana Shimizu, Minako Ito, Takashi Shichita, Rimpei Morita, Hayato Takahashi, Masayuki Amagai, Akihiko Yoshimura |
| Journal | Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 191 Issue 6 Pg. 3065-72 (Sep 15 2013) ISSN: 1550-6606 [Electronic] United States |
| PMID | 23956432 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!