Th17 cells carrying TCR recognizing epidermal autoantigen induce psoriasis-like skin inflammation

S Nishimoto, H Kotani, S Tsuruta, N Shimizu… - The Journal of …, 2013 - journals.aai.org
S Nishimoto, H Kotani, S Tsuruta, N Shimizu, M Ito, T Shichita, R Morita, H Takahashi…
The Journal of Immunology, 2013journals.aai.org
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 …
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.
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