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.

• Antibodies
• autoimmune response
• cytokines
• forkhead transcription factor 3
• glomerulonephritis

Acknowledgements

This study was supported by the Dr. Kikuchi Masahiro, former president of Kyorinkai Murakami Memorial Hospital and former associate chancellor of Fukuoka University; we are eternally grateful for his many kindnesses and we extend our condolences to his family and colleagues at his demise.