Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritis |
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Authors: | Singh Ram Raj Saxena Vijay Zang Song Li Lily Finkelman Fred D Witte David P Jacob Chaim O |
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Affiliation: | University of Cincinnati College of Medicine, Department of Internal Medicine, Veterans Affairs Medical Center and Children's Medical Center, Cincinnati, OH 45220, USA. |
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Abstract: | Mechanisms that initiate lupus nephritis and cause progression to end-stage renal disease remain poorly understood. In this study, we show that lupus-prone New Zealand Mixed 2410 mice that develop a severe glomerulosclerosis and rapidly progressive renal disease overexpress IL-4 in vivo. In these mice, STAT6 deficiency or anti-IL-4 Ab treatment decreases type 2 cytokine responses and ameliorates kidney disease, particularly glomerulosclerosis, despite the presence of high levels of IgG anti-dsDNA Abs. STAT4 deficiency, however, decreases type 1 and increases type 2 cytokine responses, and accelerates nephritis, in the absence of high levels of IgG anti-dsDNA Abs. Thus, STAT6 and IL-4 may selectively contribute to the development of glomerulosclerosis, whereas STAT4 may play a role in autoantibody production. |
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