title: Overexpression of Epstein-Barr virus-induced gene 3 protein (EBI3) in MRL/lpr mice suppresses their lupus nephritis by activating regulatory T cells.
abstract: To identify the effect of an imbalance of Th1/Th2 cytokines on the development of autoimmune glomerulonephritis (lupus nephritis), we studied the modification of pathological changes in diffuse proliferative glomerulonephritis (DPGN) and membranous glomerulonephritis (MGN) in MRL/lpr mice, which are animal models of systemic lupus erythematosus (SLE). Transgenic MRL/lpr mice (Tg) that overexpressed Epstein--Barr virus-induced gene 3 (EBI3) showed almost normal renal function, which was demonstrated by healing of glomerulonephritis upon renal histology, as compared to the wild-type MRL/lpr (Wt) mice. The levels of anti-dsDNA antibodies and IgE decreased in the Tg mice compared to Wt mice. Quantitative real-time PCR indicated an increase in the mRNA levels of FoxP3, and a decrease in that of IFNγ in the splenocytes of Tg mice as compared to Wt mice. In addition, flow cytometric analysis showed an increase in CD4(+)CD25(+)FoxP3(+)-T cells in the former, as compared to the latter. Our findings suggest that EBI3-overexpression in MRL/lpr mice induces generation of regulatory T cells, which causes suppression of autoimmune and inflammatory reactions by affecting the Th1/Th2 cytokine balance.
authors.affiliation: Department of Internal Medicine and.
authors.forename: Nishimura
authors.initials: N
authors.lastname: Shinsuke
authors.forename: Inoue
authors.initials: I
authors.lastname: Hiroshi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; C097732:EBI3 protein, human; D007378:Interleukins; D015778:Minor Histocompatibility Antigens