TLR-mediated up-regulation of serum retroviral gp70 is controlled by the Sgp loci of lupus-prone mice.
TLR-mediated up-regulation of serum retroviral gp70 is controlled by the Sgp loci of lupus-prone mice.
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DOI：
10.1016/j.jaut.2010.06.001
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发表时间：
2010-09
影响因子：
12.8
通讯作者：
Izui S
中科院分区：
文献类型：
--
作者：
Baudino L;Yoshinobu K;Dunand-Sauthier I;Evans LH;Izui S
与小鼠系统性红斑狼疮 (SLE) 相关的内源性逆转录病毒包膜糖蛋白 gp70，被认为是异向性、多向性 (PT) 和修饰 PT (mPT) 内源性逆转录病毒的产物。它像急性期蛋白一样由肝细胞分泌，但其反应受到遗传控制。鉴于 TLR7 和 TLR9 在 SLE 发病机制中的关键作用，我们评估了它们对血清 gp70 急性期表达的贡献，并确定了 Sgp3（血清 gp70 产生 3）和 Sgp4 位点在此反应中的关键作用。我们的结果表明，在注射 TLR7 或 TLR9 激动剂的狼疮倾向 NZB 小鼠中，gp70 的血清水平上调，其水平与注射 IL-1、IL-6 或 TNF 诱导的水平相当。此外，对 C57BL/6 Sgp3 和/或 Sgp4 同类小鼠的研究确定了这两个基因座在急性期反应期间上调血清 gp70 产生的主要作用。最后，对Sgp3同系小鼠的分析强烈表明，在Sgp3区间存在至少两种不同的遗传因素，其中一个控制异种、PT和mPT gp70的基础水平表达，另一个控制急性期反应期间异种和mPT gp70的上调产生。我们的结果揭示了 TLR7 和 TLR9 通过促进肾炎性 gp70 自身抗原的表达而在小鼠狼疮性肾炎中发挥额外的致病作用。此外，他们还揭示了狼疮易发小鼠在稳态和炎症条件下 gp70 自身抗原表达的多个调控基因的参与。
The endogenous retroviral envelope glycoprotein, gp70, implicated in murine systemic lupus erythematosus (SLE), has been considered to be a product of xenotropic, polytropic (PT) and modified PT (mPT) endogenous retroviruses. It is secreted by hepatocytes like an acute phase protein, but its response is under a genetic control. Given critical roles of TLR7 and TLR9 in the pathogenesis of SLE, we assessed their contribution to the acute phase expression of serum gp70, and defined a pivotal role of the Sgp3 (serum gp70 production 3) and Sgp4 loci in this response. Our results demonstrated that serum levels of gp70 were up-regulated in lupus-prone NZB mice injected with TLR7 or TLR9 agonist at levels comparable to those induced by injection of IL-1, IL-6 or TNF. In addition, studies of C57BL/6 Sgp3 and/or Sgp4 congenic mice defined the major roles of these two loci in up-regulated production of serum gp70 during acute phase responses. Finally, the analysis of Sgp3 congenic mice strongly suggests the presence of at least two distinct genetic factors in the Sgp3 interval, one of which controlled the basal-level expression of xenotropic, PT and mPT gp70 and the other which controlled the up-regulated production of xenotropic and mPT gp70 during acute phase responses. Our results uncovered an additional pathogenic role of TLR7 and TLR9 in murine lupus nephritis by promoting the expression of nephritogenic gp70 autoantigen. Furthermore, they revealed the involvement of multiple regulatory genes for the expression of gp70 autoantigen under steady-state and inflammatory conditions in lupus-prone mice.
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影响因子：
4.8
作者：
Bulliard, Yannick;Wiznerowicz, Maciej;Trono, Didier
通讯作者：
Trono, Didier
遗传机制的解剖，涉及与鼠狼疮炎有关的血清逆转录病毒GP70的表达。
影响因子：
4.4
作者：
Baudino, Lucie;Yoshinobu, Kumiko;Morito, Naoki;Kikuchi, Shuichi;Fossati-Jimack, Liliane;Morley, Bernard J.;Vyse, Timothy J.;Hirose, Sachiko;Jorgensen, Trine N.;Tucker, Rebecca M.;Roark, Christina L.;Kotzin, Brian L.;Evans, Leonard H.;Izui, Shozo
通讯作者：
Izui, Shozo
影响因子：
64.8
作者：
ELDER, JH;JENSEN, FC;LERNER, RA
通讯作者：
LERNER, RA
影响因子：
5.4
作者：
MERINO, R;FOSSATI, L;IZUI, S
通讯作者：
IZUI, S
影响因子：
5.4
作者：
Oliver, PL;Stoye, JP
通讯作者：
Stoye, JP