Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis.
Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis.
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DOI：
10.1007/s00401-011-0883-2
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发表时间：
2011-11
影响因子：
12.7
通讯作者：
Engelhardt B
中科院分区：
文献类型：
--
作者：
Pfeiffer F;Schäfer J;Lyck R;Makrides V;Brunner S;Schaeren-Wiemers N;Deutsch U;Engelhardt B
在实验性自身免疫性脑脊髓炎（EAE）（多发性硬化症（MS）的动物模型）中，血脑屏障（BBB）紧密连接（TJ）蛋白claudin-3的丧失与免疫细胞浸润到CNS和BBB渗漏相关。在这里，我们表明，在Tie-2 tTA//TRE-claudin-1双转基因C57 BL/6小鼠中，通过TJ蛋白claudin-1的异位四环素调节的表达来密封BBB TJ对EAE期间穿过BBB的免疫细胞运输没有影响，而且也没有影响第一次临床疾病发作的发作和严重程度。然而，紧密连接蛋白-1的表达确实显著降低了血传示踪剂和内源性血浆蛋白的BBB渗漏，特别是在表达紧密连接蛋白-1的血管周围。此外，与对照同窝出生的小鼠相比，表达紧密连接蛋白-1的小鼠在EAE的慢性期期间表现出降低的疾病负担。我们的研究确定了BBB TJ是EAE期间调节BBB通透性的关键结构，但不是免疫细胞运输到CNS中，并表明BBB功能障碍是EAE慢性期疾病负担的潜在关键事件。我们的观察结果表明，稳定BBB屏障功能的治疗靶向的TJ可能是有益的治疗MS，特别是当抗炎治疗失败。本文的在线版本（doi：10.1007/s 00401 -011-0883-2）包含补充材料，可供授权用户使用。
In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood–brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition, mice expressing claudin-1 exhibited a reduced disease burden during the chronic phase of EAE as compared to control littermates. Our study identifies BBB TJs as the critical structure regulating BBB permeability but not immune cell trafficking into CNS during EAE, and indicates BBB dysfunction is a potential key event contributing to disease burden in the chronic phase of EAE. Our observations suggest that stabilizing BBB barrier function by therapeutic targeting of TJs may be beneficial in treating MS, especially when anti-inflammatory treatments have failed. The online version of this article (doi:10.1007/s00401-011-0883-2) contains supplementary material, which is available to authorized users.
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影响因子：
7.8
作者：
Furuse, Mikio;Hata, Masaki;Furuse, Kyoko;Yoshida, Yoko;Haratake, Akinori;Sugitani, Yoshinobu;Noda, Tetsuo;Kubo, Akiharu;Tsukita, Shoichiro
通讯作者：
Tsukita, Shoichiro
单个基因产物Claudin -1或-2，在成纤维细胞中重构紧密结合的连接链和新兵。
影响因子：
7.8
作者：
Furuse, M;Sasaki, H;Fujimoto, K;Tsukita, S
通讯作者：
Tsukita, S
紧密连接链内和之间异质claudin物种相互作用的方式。
影响因子：
7.8
作者：
Furuse, M;Sasaki, H;Tsukita, S
通讯作者：
Tsukita, S
DOI：
10.1073/pnas.0701252104
发表时间：
2007-03-27
影响因子：
11.1
作者：
Fabis, Marzena J.;Scott, Gwen S.;Hooper, D. Craig
通讯作者：
Hooper, D. Craig
影响因子：
3.7
作者：
Daneman R;Zhou L;Agalliu D;Cahoy JD;Kaushal A;Barres BA
通讯作者：
Barres BA