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

Summary 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.