title: T cell-specific overexpression of interleukin-27 receptor α subunit (WSX-1) prevents spontaneous skin inflammation in MRL/lpr mice.
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).
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kido
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: N
authors.initials: N
authors.lastname: Sugiyama
authors.forename: H
authors.initials: H
authors.lastname: Esaki
authors.forename: H
authors.initials: H
authors.lastname: Nakashima
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Furue
mesh_terms: D000818:Animals; D003872:Dermatitis / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000378:metabolism*; D018123:Receptors, Interleukin; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: C484747:Il27ra protein, mouse; D007074:Immunoglobulin G; D020381:Interleukin-17; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin