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

Takashi Igawa, Hitoshi Nakashima, Atsushi Sadanaga, Kohsuke Masutani, Katsuhisa Miyake, Sakiko Shimizu, Atsunobu Takeda, Shinjiro Hamano, Hiroki Yoshida

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Abstract

MRL/lpr mice develop a systemic autoimmune disease that is reminiscent of systemic lupus erythematosus (SLE) and Sjögren'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 Sjögren'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.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalModern Rheumatology
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 1 2009

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Inbred MRL lpr Mouse
Sialadenitis
Glomerulonephritis
Human Herpesvirus 4
Interleukin-27
Immunoglobulin G
Genes
Autoimmune Diseases
Th1-Th2 Balance
Membranous Glomerulonephritis
Plasma Cells
Salivary Glands
Autoimmunity
Interleukin-4
Systemic Lupus Erythematosus
Immunoglobulin E
T-Lymphocytes
Phenotype
Serum

All Science Journal Classification (ASJC) codes

  • Rheumatology

Cite this

Deficiency in EBV-induced gene 3 (EBI3) in MRL/lpr mice results in pathological alteration of autoimmune glomerulonephritis and sialadenitis. / Igawa, Takashi; Nakashima, Hitoshi; Sadanaga, Atsushi; Masutani, Kohsuke; Miyake, Katsuhisa; Shimizu, Sakiko; Takeda, Atsunobu; Hamano, Shinjiro; Yoshida, Hiroki.

In: Modern Rheumatology, Vol. 19, No. 1, 01.01.2009, p. 33-41.

Research output: Contribution to journalArticle

Igawa, T, Nakashima, H, Sadanaga, A, Masutani, K, Miyake, K, Shimizu, S, Takeda, A, Hamano, S & Yoshida, H 2009, 'Deficiency in EBV-induced gene 3 (EBI3) in MRL/lpr mice results in pathological alteration of autoimmune glomerulonephritis and sialadenitis', Modern Rheumatology, vol. 19, no. 1, pp. 33-41. https://doi.org/10.1007/s10165-008-0117-1
Igawa, Takashi ; Nakashima, Hitoshi ; Sadanaga, Atsushi ; Masutani, Kohsuke ; Miyake, Katsuhisa ; Shimizu, Sakiko ; Takeda, Atsunobu ; Hamano, Shinjiro ; Yoshida, Hiroki. / Deficiency in EBV-induced gene 3 (EBI3) in MRL/lpr mice results in pathological alteration of autoimmune glomerulonephritis and sialadenitis. In: Modern Rheumatology. 2009 ; Vol. 19, No. 1. pp. 33-41.
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