Therapeutic effect of leflunomide on the development of experimental lupus nephritis in mice
Therapeutic effect of leflunomide on the development of experimental lupus nephritis in mice
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DOI：
10.1007/s00296-010-1630-z
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发表时间：
2012-03-01
影响因子：
4
通讯作者：
Luo, Ping
中科院分区：
文献类型：
--
作者：
He, Chunyan;Lu, Xuehong;Luo, Ping
通过将亲本 BALB/C 淋巴细胞转移至 (C57BL/6 x BALB/C) F1 (CBF1) 杂交种而诱导患有慢性移植物抗宿主病 (cGVHD) 的小鼠，会出现一种以 B 细胞过度活跃、自身抗体产生和免疫复合物介导的肾小球肾炎为特征的综合征。在此模型中，我们评估了来氟米特在系统自身免疫中狼疮性肾炎发展中的作用。从cGVHD诱导后2周起每天服用来氟米特（15 mg/kg/d）可以显着减少自身抗体的产生和肾脏中免疫复合物的沉积，从而减轻肾脏损伤并降低死亡率。来氟米特对狼疮易感小鼠的治疗作用部分归因于TLR9信号通路的抑制，TLR9信号通路是先天免疫系统的重要组成部分。
Mice with chronic graft-versus-host disease (cGVHD) induced by transferring parental BALB/C lymphocytes into (C57BL/6 x BALB/C) F1 (CBF1) hybrids, develop a syndrome characterized by B-cell hyperactivity, autoantibody production, and immune complex-mediated glomerulonephritis. In this model, we evaluated the role of leflunomide on the development of lupus nephritis in system autoimmunity. Daily administration of leflunomide (15 mg/kg/d) from 2 weeks after cGVHD induction can dramatically reduce the production of autoantibodies and immune complex deposition in the kidney, leading to relieved kidney damage and reduced mortality. The therapeutic effect of leflunomide on the lupus-prone mice was partially due to the inhibition of TLR9 signaling pathway, which was an important component of innate immune system.