T cell-specific overexpression of interleukin-27 receptor α subunit (WSX-1) prevents spontaneous skin inflammation in MRL/lpr mice

M. Kido, S. Takeuchi, N. Sugiyama, H. Esaki, H. Nakashima, H. Yoshida, M. Furue

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background Interleukin (IL)-27 and WSX-1, the receptor α-specific subunit, have been shown to play important roles in initiating Th1 responses and in inducing immune modulation, and the immunosuppressive effect of IL-27 appears to be exerted via suppression of IL-10 and IL-17, which may participate in the pathogenesis of human systemic lupus erythematosus (SLE). Objectives To examine the significance of IL-27/WSX-1 signalling in spontaneous skin inflammation of MRL/lpr mice, a model for SLE. Methods The severity and development of skin lesions, dermal inflammatory cells and epidermal-dermal depositions in the skin lesions of MRL/lpr mice with CD2-promoted WSX-1 overexpression (WSX-1 Tg mice) and those with globally disrupted WSX-1 (WSX-1 KO mice) were examined and compared with those of MRL/lpr mice. Results By 4 months of age, both WSX-1 KO mice and control MRL/lpr mice developed predominantly similar skin inflammation, while WSX-1 Tg mice hardly did so, demonstrating that intensifying IL-27/WSX-1 signalling on T cells prevents the spontaneous skin inflammation. WSX-1 KO mice showed Th2-type skin inflammation as evidenced by the Th2-prone dermal infiltrating cells and an absence of cutaneous Th1-type IgG deposition. Interestingly, there were significant IL-17+ dermal infiltrating cells in both WSX-1 KO and control MRL/lpr mice, which might potentially contribute to the formation of skin inflammation in these mice. Conclusions These data indicate that IL-27/WSX-1 signalling may play a protective role in the development of SLE-like skin inflammation, and modulating IL-27/WSX-1 signalling might be an interesting therapeutic strategy in the treatment of SLE.

Original languageEnglish
Pages (from-to)1214-1220
Number of pages7
JournalBritish Journal of Dermatology
Volume164
Issue number6
DOIs
Publication statusPublished - Jun 1 2011

All Science Journal Classification (ASJC) codes

  • Dermatology

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