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

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)7185-7192
Number of pages8
JournalJournal of Immunology
Issue number11
Publication statusPublished - Dec 1 2005

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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