A truncated IL-12rβ1 receptor ameliorates chronic graft-versus-host disease-induced lupus nephritis by inhibiting Th1 and Th17 cells

被引：4
|
作者：
Wang, Chen [1 ]
Guo, Wei [1 ]
Cai, Di [1 ]
Wang, Xin [1 ]
Yu, Dongmei [1 ]
Gao, Xiangdong [1 ]
Yao, Wenbing [1 ]
机构：
[1] China Pharmaceut Univ, Sch Life Sci & Technol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY | 2015年 / 29卷 / 02期
基金：
中国国家自然科学基金;
关键词：
IL-17; IL-23R; Lupus nephritis; Chronic graft-versus host disease; ERYTHEMATOSUS; IL-23; IL-17; MICE;
D O I：
10.1016/j.intimp.2015.09.030
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Th1 and Th17 cells have been strongly implicated in the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-12 and IL-23 respectively drive the polarization of Th1 and Th17 cells and share a common p40 subunit. In this study, the protective and therapeutic effects of a truncated human IL-12r beta 1 receptor (tIL12r beta 1) targeting IL-12/IL-23 p40 were evaluated in chronic graft-versus-host disease (cGVHD)-induced SLE-like model. The results indicated that tIL12r beta 1 treatment effectively delayed the proteinuria onset and induced a significant remission of proteinuria, autoantibody production, and immune complex deposition in the mouse model. Remarkably, the therapeutic effects of tIL12r beta 1 were predominantly dependent on the suppression of pathogenic Th1 and Th17 cell commitment through the reduction of ROR gamma t and T-bet expression. Collectively, this receptor molecule may offer a new treatment option for SLE. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码：544 / 551
页数：8
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