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Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of IL-27Rα (WSX-1)
  1. Naonobu Sugiyama (nao1{at}intmed1.med.kyushu-u.ac.jp)
  1. Graduate School of Medical Sciences, Kyushu University, Japan
    1. Hitoshi Nakashima (hnakashi{at}fukuoka-u.ac.jp)
    1. Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University, Japan
      1. Takeru Yoshimura (takeruy{at}bioreg.kyushu-u.ac.jp)
      1. Graduate School of Medical Sciences, Kyushu University, Japan
        1. Atsushi Sadanaga (sadanaga{at}qd5.so-net.ne.jp)
        1. Graduate School of Medical Sciences, Kyushu University, Japan
          1. Sakiko Shimizu (sakiko{at}intmed1.med.kyushu-u.ac.jp)
          1. Graduate School of Medical Sciences, Kyushu University, Japan
            1. Kohsuke Masutani (km0123{at}alles.or.jp)
            1. Graduate School of Medical Sciences, Kyushu University, Japan
              1. Takashi Igawa (t-igawa{at}intmed1.med.kyushu-u.ac.jp)
              1. Graduate School of Medical Sciences, Kyushu University, Japan
                1. Mitsuteru Akahoshi (akahoshi{at}med.kyushu-u.ac.jp)
                1. Graduate School of Medical Sciences, Kyushu University, Japan
                  1. Katsuhisa Miyake
                  1. Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University, Japan
                    1. Atsunobu Takeda
                    1. Graduate School of Medical Sciences, Kyushu University, Japan
                      1. Akihiko Yoshimura
                      1. Medical Institute of Bioregulation, Kyushu University, Japan
                        1. Shinjiro Hamano (hamano{at}parasite.med.kyushu-u.ac.jp)
                        1. Graduate School of Medical Sciences, Kyushu University, Japan
                          1. Hiroki Yoshida (yoshidah{at}med.saga-u.ac.jp)
                          1. Faculty of Medicine, Saga University, Japan

                            Abstract

                            Objective: Investigation of the role of IL-27/IL-27Rα (WSX-1) in the development of autoimmune disorders in MRL/lpr mouse, which is considered as an experimental model of systemic lupus erythematosus in humans.

                            Methods: We generated two strains of WSX-1 transgenic mice in the MRL/lpr background (WSX-1 Tg High MRL/lpr mice and WSX-1Tg Low MRL/lpr mice) with different expression levels of WSX-1, and investigated the effect of WSX-1 overexpression on survival, glomerulonephritis, and immunological properties.

                            Results: In comparison with wild-type MRL/lpr(WT) and Tg Low (TgL) mice, Tg High(TgH) mice exhibited a prolonged lifespan and no apparent development of autoimmune nephritis. Production of anti-dsDNA antibody and total IgG and IgG2a were significantly lower in TgH mice than those of TgL and WT mice. The expressed amounts of IFN-γ and IL-4 mRNA by CD4+ T cells from Tg mice decreased in a dose-dependent fashion. CD4+ splenic lymphocytes in TgH mice were more subject to the IL-27-mediated suppression of cytokine production. In vitro stimulation of CD4+ T cells by IL-27 resulted in over phosphorylation of STAT3 in TgH cells than in WT cells.

                            Conclusion: WSX-1 over-expression in the MRL/lpr background rendered the autoimmune prone mice protected from the development of autoimmune diseases.Our results suggest that IL-27 signal may be a therapeutic target against autoimmune diseases including human SLE.

                            • IL-27/WSX-1
                            • MRL/lpr mice
                            • SLE
                            • autoimmune disease

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