In hepatic fibrosis, liver sinusoidal endothelial cells acquire enhanced immunogenicity.
In hepatic fibrosis, liver sinusoidal endothelial cells acquire enhanced immunogenicity.
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DOI：
10.4049/jimmunol.1000332
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发表时间：
2010-08-15
期刊：
影响因子：
--
通讯作者：
Miller G
中科院分区：
文献类型：
--
作者：
Connolly MK;Bedrosian AS;Malhotra A;Henning JR;Ibrahim J;Vera V;Cieza-Rubio NE;Hassan BU;Pachter HL;Cohen S;Frey AB;Miller G
正常肝脏的特征是免疫耐受。肝脏免疫耐受的主要介质是肝窦内皮细胞（LSEC）。LSEC阻断对Ag的适应性免疫原性应答并诱导调节性T细胞的产生。肝纤维化的特征是强烈的肝内炎症和肝脏免疫改变。我们推测，在肝纤维化中，LSEC功能从致耐受性逆转为促炎性和免疫原性可能有助于炎症环境的增强和肝内免疫的改变。我们发现，在肝毒素引起的肝纤维化损伤后，LSEC变得高度促炎并分泌一系列细胞因子和趋化因子。此外，LSEC获得增强的捕获Ag和诱导T细胞增殖的能力。类似地，与正常肝脏中的LSEC不同，在纤维化中，LSEC不否决T细胞的树突状细胞引发。此外，在正常肝脏中，LSEC在T调节细胞的产生中是有活性的，而在肝纤维化中，LSEC诱导能够增强内源性CTL并产生有效的从头CTL应答的免疫原性T细胞表型。此外，从纤维化肝培养物中消耗LSEC减轻了肝纤维化的促炎环境特征。我们的研究结果提供了一个关键的了解LSECs在调节肝内免疫和炎症的纤维炎症性肝病的作用。
The normal liver is characterized by immunologic tolerance. Primary mediators of hepatic immune tolerance are liver sinusoidal endothelial cells (LSECs). LSECs block adaptive immunogenic responses to Ag and induce the generation of T regulatory cells. Hepatic fibrosis is characterized by both intense intrahepatic inflammation and altered hepatic immunity. We postulated that, in liver fibrosis, a reversal of LSEC function from tolerogenic to proinflammatory and immunogenic may contribute to both the heightened inflammatory milieu and altered intrahepatic immunity. We found that, after fibrotic liver injury from hepatotoxins, LSECs become highly proinflammatory and secrete an array of cytokines and chemokines. In addition, LSECs gain enhanced capacity to capture Ag and induce T cell proliferation. Similarly, unlike LSECs in normal livers, in fibrosis, LSECs do not veto dendritic cell priming of T cells. Furthermore, whereas in normal livers, LSECs are active in the generation of T regulatory cells, in hepatic fibrosis LSECs induce an immunogenic T cell phenotype capable of enhancing endogenous CTLs and generating potent de novo CTL responses. Moreover, depletion of LSECs from fibrotic liver cultures mitigates the proinflammatory milieu characteristic of hepatic fibrosis. Our findings offer a critical understanding of the role of LSECs in modulating intrahepatic immunity and inflammation in fibro-inflammatory liver disease.
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影响因子：
32.4
作者：
Goubier, Anne;Dubois, Bertrand;Gheit, Hanane;Joubert, Grgoire;Villard-Truc, Florence;Asselin-Paturel, Carine;Trinchieri, Giorgio;Kaiserlian, Dominique
通讯作者：
Kaiserlian, Dominique
影响因子：
4.8
作者：
Kriegs, Malte;Buerckstuemmer, Tilmann;Hildt, Eberhard
通讯作者：
Hildt, Eberhard
影响因子：
4.4
作者：
Katz, SC;Pillarisetty, VG;DeMatteo, RP
通讯作者：
DeMatteo, RP
影响因子：
4.4
作者：
Pillarisetty, VG;Shah, AB;DeMatteo, RP
通讯作者：
DeMatteo, RP
DOI：
10.4049/jimmunol.0901564
发表时间：
2009-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Yeligar SM;Machida K;Tsukamoto H;Kalra VK
通讯作者：
Kalra VK