Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1)

Sakiko Shimizu, Naonobu Sugiyama, Kohsuke Masutani, Atsushi Sadanaga, Yoshiyuki Miyazaki, Yasushi Inoue, Mitsuteru Akahoshi, Ritsuko Katafuchi, Hideki Hirakata, Mine Harada, Shinjiro Hamano, Hitoshi Nakashima, Hiroki Yoshida

研究成果: ジャーナルへの寄稿記事

89 引用 (Scopus)

抄録

MKL/lpr mice develop spontaneous glomerulonephritis that is essentially identical with diffuse proliferative glomerulonephritis (World Health Organization class IV) in human lupus nephritis, Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. Diffuse proliferative glomerulonephritis is associated with autoimmune responses dominated by Th1 cells producing high levels of IFN-γ. The initial mounting of Th1 responses depends on the function of the WSX-1 gene, which encodes a subunit of the IL-27R with homology to IL-12R. In mice deficient for the WSX-1 gene, proper Th1 differentiation was impaired and abnormal Th2 skewing was observed during infection with some intracellular pathogens. Disruption of the WSX-1 gene dramatically changed the pathophysiology of glomerulonephritis developing in MRL/lpr mice, WSX-1-/- MRL/lpr mice developed disease resembling human membranous glomerulonephritis (World Health Organization class V) with a predominance of IgG1 in glomerular deposits, accompanied by increased IgG1 and IgE in the sera. T cells in WSX-1 -/- MKL/lpr mice displayed significantly reduced IFN-γ production along with elevated IL-4 expression. Loss of WSX-1 thus favors Th2-type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal determinant of human lupus nephritis development.

元の言語英語
ページ(範囲)7185-7192
ページ数8
ジャーナルJournal of Immunology
175
発行部数11
DOI
出版物ステータス出版済み - 12 1 2005

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Interleukin-27
Inbred MRL lpr Mouse
Membranous Glomerulonephritis
Glomerulonephritis
Lupus Nephritis
Autoimmunity
Immunoglobulin G
Th1-Th2 Balance
Genes
Th1 Cells
Interleukin-4
Systemic Lupus Erythematosus
Immunoglobulin E
T-Lymphocytes
Infection
Serum

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

これを引用

Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1). / Shimizu, Sakiko; Sugiyama, Naonobu; Masutani, Kohsuke; Sadanaga, Atsushi; Miyazaki, Yoshiyuki; Inoue, Yasushi; Akahoshi, Mitsuteru; Katafuchi, Ritsuko; Hirakata, Hideki; Harada, Mine; Hamano, Shinjiro; Nakashima, Hitoshi; Yoshida, Hiroki.

:: Journal of Immunology, 巻 175, 番号 11, 01.12.2005, p. 7185-7192.

研究成果: ジャーナルへの寄稿記事

Shimizu, S, Sugiyama, N, Masutani, K, Sadanaga, A, Miyazaki, Y, Inoue, Y, Akahoshi, M, Katafuchi, R, Hirakata, H, Harada, M, Hamano, S, Nakashima, H & Yoshida, H 2005, 'Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1)', Journal of Immunology, 巻. 175, 番号 11, pp. 7185-7192. https://doi.org/10.4049/jimmunol.175.11.7185
Shimizu, Sakiko ; Sugiyama, Naonobu ; Masutani, Kohsuke ; Sadanaga, Atsushi ; Miyazaki, Yoshiyuki ; Inoue, Yasushi ; Akahoshi, Mitsuteru ; Katafuchi, Ritsuko ; Hirakata, Hideki ; Harada, Mine ; Hamano, Shinjiro ; Nakashima, Hitoshi ; Yoshida, Hiroki. / Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1). :: Journal of Immunology. 2005 ; 巻 175, 番号 11. pp. 7185-7192.
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abstract = "MKL/lpr mice develop spontaneous glomerulonephritis that is essentially identical with diffuse proliferative glomerulonephritis (World Health Organization class IV) in human lupus nephritis, Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. Diffuse proliferative glomerulonephritis is associated with autoimmune responses dominated by Th1 cells producing high levels of IFN-γ. The initial mounting of Th1 responses depends on the function of the WSX-1 gene, which encodes a subunit of the IL-27R with homology to IL-12R. In mice deficient for the WSX-1 gene, proper Th1 differentiation was impaired and abnormal Th2 skewing was observed during infection with some intracellular pathogens. Disruption of the WSX-1 gene dramatically changed the pathophysiology of glomerulonephritis developing in MRL/lpr mice, WSX-1-/- MRL/lpr mice developed disease resembling human membranous glomerulonephritis (World Health Organization class V) with a predominance of IgG1 in glomerular deposits, accompanied by increased IgG1 and IgE in the sera. T cells in WSX-1 -/- MKL/lpr mice displayed significantly reduced IFN-γ production along with elevated IL-4 expression. Loss of WSX-1 thus favors Th2-type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal determinant of human lupus nephritis development.",
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AU - Masutani, Kohsuke

AU - Sadanaga, Atsushi

AU - Miyazaki, Yoshiyuki

AU - Inoue, Yasushi

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AU - Katafuchi, Ritsuko

AU - Hirakata, Hideki

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