Deficiency in EBV-induced gene 3 (EBI3) in MRL/lpr mice results in pathological alteration of autoimmune glomerulonephritis and sialadenitis.
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-gamma 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.
Igawa
Takashi
T
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Nakashima
Hitoshi
H
Sadanaga
Atsushi
A
Masutani
Kohsuke
K
Miyake
Katsuhisa
K
Shimizu
Sakiko
S
Takeda
Atsunobu
A
Hamano
Shinjiro
S
Yoshida
Hiroki
H
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015551:Autoimmunity / Q000276:immunology*; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D015433:Glomerulonephritis, Membranous / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000172:deficiency* / Q000235:genetics; D012793:Sialadenitis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C499601:Ebi3 protein, mouse; D007074:Immunoglobulin G; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D004247:DNA