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Published on: January 25, 2017
T cell-specific overexpression of interleukin-27 receptor α subunit (WSX-1) prevents spontaneous skin inflammation in
M Kido1, S Takeuchi, N Sugiyama
1Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
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.
