Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritis
Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritis
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DOI：
10.4049/jimmunol.170.9.4818
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发表时间：
2003-05-01
影响因子：
4.4
通讯作者：
Jacob, CO
中科院分区：
文献类型：
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作者：
Singh, RR;Saxena, V;Jacob, CO
引发狼疮性肾炎并导致进展为终末期肾病的机制仍知之甚少。在这项研究中，我们发现易患狼疮的新西兰混合 2410 只小鼠出现严重肾小球硬化症和快速进展性肾病，体内过度表达 IL-4。在这些小鼠中，尽管存在高水平的 IgG 抗 dsDNA 抗体，但 STAT6 缺陷或抗 IL-4 抗体治疗可降低 2 型细胞因子反应并改善肾脏疾病，特别是肾小球硬化症。然而，在缺乏高水平 IgG 抗 dsDNA 抗体的情况下，STAT4 缺陷会降低 1 型细胞因子反应并增加 2 型细胞因子反应，并加速肾炎。因此，STAT6和IL-4可能选择性地促进肾小球硬化的发展，而STAT4可能在自身抗体的产生中发挥作用。
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.