Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis.
Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis.
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DOI：
10.1016/j.immuni.2012.08.014
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发表时间：
2012-12-14
期刊：
影响因子：
32.4
通讯作者：
Siebenlist U
中科院分区：
文献类型：
--
作者：
Pisitkun P;Ha HL;Wang H;Claudio E;Tivy CC;Zhou H;Mayadas TN;Illei GG;Siebenlist U
系统性红斑狼疮是一种潜在的致命性自身免疫性疾病。虽然白细胞介素-17（IL-17）与人类狼疮和这种疾病的小鼠模型有关，但尚未解决这种细胞因子是否在致命的狼疮病理学中起关键作用。在这里，我们已经证明了IL-17细胞因子的产生增加以及它们通过衔接蛋白CIKS（a.k.a. Traf 3 ip 2，Act 1）在FcgammaR 2b缺陷型狼疮小鼠模型中对致死性病理学有重要贡献。缺乏IL-17的小鼠，尤其是缺乏CIKS的小鼠，存活率大大提高，并在很大程度上免受肾小球肾炎的发展。重要的是，在该模型中，IL-17细胞因子对抗体产生的潜在影响可以与肾脏中的关键局部贡献（包括中性粒细胞和单核细胞的募集）区分开来。这些发现提供了原理证据，即通过CIKS介导的IL-17家族细胞因子的信号传导为系统性红斑狼疮的治疗提供了有希望的治疗靶点，特别是在肾脏受累的情况下。
Systemic lupus erythematosus is a potentially fatal autoimmune disease. Although interleukin-17 (IL-17) has been linked to human lupus and mouse models of this disease, it has not been addressed whether this cytokine plays a critical role in fatal lupus pathology. Here we have demonstrated that increased production of IL-17 cytokines and their signaling via the adaptor protein CIKS (a.k.a. Traf3ip2, Act1) critically contributed to lethal pathology in an FcgammaR2b-deficient mouse model of lupus. Mice lacking IL-17 and especially those lacking CIKS showed greatly improved survival and were largely protected from development of glomerulonephritis. Importantly in this model, potential effects of IL-17 cytokines on antibody production could be distinguished from critical local contributions in kidneys, including recruitment of neutrophils and monocytes. These findings provide the proof of principle that signaling by IL-17 family cytokines mediated via CIKS presents promising therapeutic targets for the treatment of systemic lupus erythematosus, especially in cases with kidney involvement.
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影响因子：
32.4
作者：
Oppmann, B;Lesley, R;Kastelein, RA
通讯作者：
Kastelein, RA
影响因子：
4.4
作者：
Claudio, Estefania;Sonder, Soren Ulrik;Saret, Sun;Carvalho, Gabrielle;Ramalingam, Thirumalai R.;Wynn, Thomas A.;Chariot, Alain;Garcia-Perganeda, Antonio;Leonardi, Antonio;Paun, Andrea;Chen, Amy;Ren, Nina Y.;Wang, Hongshan;Siebenlist, Ulrich
通讯作者：
Siebenlist, Ulrich
影响因子：
30.5
作者：
Doreau, Agnes;Belot, Alexandre;Bonnefoy-Berard, Nathalie
通讯作者：
Bonnefoy-Berard, Nathalie
影响因子：
5.8
作者：
Matusevicius, D;Kivisäkk, P;Link, H
通讯作者：
Link, H
DOI：
10.1111/j.1749-6632.1997.tb52046.x
发表时间：
1997-01-01
期刊：
B LYMPHOCYTES AND AUTOIMMUNITY
影响因子：
--
作者：
Chan, O;Madaio, MP;Shlomchik, MJ
通讯作者：
Shlomchik, MJ