Vol.19 No.1

Original Article

Deficiency in EBV-induced gene 3 (EBI3) in MRL/ lpr mice results in pathological alteration of autoimmune glomerulonephritis and sialadenitis

Authors

Takashi Igawa1 , Hitoshi Nakashima5 , Atsushi Sadanaga1 , Kohsuke Masutani2 , Katsuhisa Miyake5 , Sakiko Shimizu1 , Atsunobu Takeda3 , Shinjiro Hamano4 , Hiroki Yoshida6

  • Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
  • Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
  • Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
  • Department of Parasitology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
  • Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonann-ku, Fukuoka 814-0180, Japan
  • Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan
Received:

21 May 2008

Accepted:

17 July 2008

Published online:

10 September 2008

Full Text

PDF　(member's only)

Abstract

MRL/lpr mice develop a systemic autoimmune disease that is reminiscent of systemic lupus erythematosus (SLE) and Sj?gren’s syndrome in humans. To investigate the role of IL-27 in the development of autoimmune disorders in MRL/lpr mice, we disrupted the EBV-induced gene 3 (EBI3), which is a subunit of IL-27. Consequently, the pathophysiology of glomerulonephritis and sialadenitis, which develops in MRL/lpr mice, was drastically changed. EBI3-/- MRL/lpr mice developed disease that resembles human membranous glomerulonephritis (MGN), not diffuse proliferative glomerulonephritis (DPGN), with a predominance of IgG1 in glomerular deposits, and different type sialadenitis from Sj?gren’s syndrome, with IgG1 producing plasma cell infiltration in salivary glands, accompanied by increased IgG1 and IgE in the sera. T cells in these mice displayed significantly reduced IFN-γ production along with elevated IL-4 expression. Loss of EBI3 thus favors Th2-type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal determinant of phenotypes of human autoimmune diseases.

Key words

EBV-induced gene 3 (EBI3) - Membranous glomerulonephritis - MRL/lpr mouse - Sialadenitis - Th1/Th2 balance