Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of interleukin 27 receptor α(WSX-1)

N. Sugiyama, H. Nakashima, T. Yoshimura, A. Sadanaga, S. Shimizu, K. Masutani, T. Igawa, M. Akahoshi, K. Miyake, A. Takeda, Akihiko Yoshimura, S. Hamano, H. Yoshida

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Abstract

Objective: In the present work, we investigate the role of interleukin (IL)27/IL27 receptor α (Rα) (WSX-1) in the development of autoimmune disorders in the MRL/lpr mouse, which is considered as an experimental model of systemic lupus erythaematosus (SLE) in humans. Methods: We generated two strains of WSX-1 transgenic mice in the MRL/lpr background 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 (WT) MRL/lpr and transgenic (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 lgG2a were significantly lower in TgH mice than those of TgL and WT mice. The expressed amounts of interferon (IFN)y and IL4 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 IL27-mediated suppression of cytokine production. In vitro stimulation of CD4+ T cells by IL27 resulted in over phosphorylation of STAT3 in TgH cells than in WT cells. Conclusion: WSX-1 overexpression in the MRL/lpr background rendered the autoimmune prone mice protected from the development of autoimmune diseases. Our results suggest that IL27 signalling may be a therapeutic target against autoimmune diseases, including human SLE.

Original languageEnglish
Pages (from-to)1461-1467
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume67
Issue number10
DOIs
Publication statusPublished - 2008 Oct
Externally publishedYes

Fingerprint

Interleukin-27
Inbred MRL lpr Mouse
Interleukin Receptors
Transgenic Mice
Phenotype
T-cells
Systemic Lupus Erythematosus
Autoimmune Diseases
T-Lymphocytes
Phosphorylation
Lymphocytes
Nephritis
Glomerulonephritis
Interleukin-4
Interferons
Anti-Idiotypic Antibodies
Theoretical Models
Immunoglobulin G
Cytokines
Messenger RNA

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Sugiyama, N., Nakashima, H., Yoshimura, T., Sadanaga, A., Shimizu, S., Masutani, K., ... Yoshida, H. (2008). Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of interleukin 27 receptor α(WSX-1). Annals of the Rheumatic Diseases, 67(10), 1461-1467. https://doi.org/10.1136/ard.2007.077537

Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of interleukin 27 receptor α(WSX-1). / Sugiyama, N.; Nakashima, H.; Yoshimura, T.; Sadanaga, A.; Shimizu, S.; Masutani, K.; Igawa, T.; Akahoshi, M.; Miyake, K.; Takeda, A.; Yoshimura, Akihiko; Hamano, S.; Yoshida, H.

In: Annals of the Rheumatic Diseases, Vol. 67, No. 10, 10.2008, p. 1461-1467.

Research output: Contribution to journalArticle

Sugiyama, N, Nakashima, H, Yoshimura, T, Sadanaga, A, Shimizu, S, Masutani, K, Igawa, T, Akahoshi, M, Miyake, K, Takeda, A, Yoshimura, A, Hamano, S & Yoshida, H 2008, 'Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of interleukin 27 receptor α(WSX-1)', Annals of the Rheumatic Diseases, vol. 67, no. 10, pp. 1461-1467. https://doi.org/10.1136/ard.2007.077537
Sugiyama, N. ; Nakashima, H. ; Yoshimura, T. ; Sadanaga, A. ; Shimizu, S. ; Masutani, K. ; Igawa, T. ; Akahoshi, M. ; Miyake, K. ; Takeda, A. ; Yoshimura, Akihiko ; Hamano, S. ; Yoshida, H. / Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of interleukin 27 receptor α(WSX-1). In: Annals of the Rheumatic Diseases. 2008 ; Vol. 67, No. 10. pp. 1461-1467.
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AU - Sadanaga, A.

AU - Shimizu, S.

AU - Masutani, K.

AU - Igawa, T.

AU - Akahoshi, M.

AU - Miyake, K.

AU - Takeda, A.

AU - Yoshimura, Akihiko

AU - Hamano, S.

AU - Yoshida, H.

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AB - Objective: In the present work, we investigate the role of interleukin (IL)27/IL27 receptor α (Rα) (WSX-1) in the development of autoimmune disorders in the MRL/lpr mouse, which is considered as an experimental model of systemic lupus erythaematosus (SLE) in humans. Methods: We generated two strains of WSX-1 transgenic mice in the MRL/lpr background 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 (WT) MRL/lpr and transgenic (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 lgG2a were significantly lower in TgH mice than those of TgL and WT mice. The expressed amounts of interferon (IFN)y and IL4 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 IL27-mediated suppression of cytokine production. In vitro stimulation of CD4+ T cells by IL27 resulted in over phosphorylation of STAT3 in TgH cells than in WT cells. Conclusion: WSX-1 overexpression in the MRL/lpr background rendered the autoimmune prone mice protected from the development of autoimmune diseases. Our results suggest that IL27 signalling may be a therapeutic target against autoimmune diseases, including human SLE.

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