Connecting liver and gut: Murine liver sinusoidal endothelium induces gut tropism of CD4+ T cells via retinoic acid
Connecting liver and gut: Murine liver sinusoidal endothelium induces gut tropism of CD4+ T cells via retinoic acid
复制标题
DOI：
10.1002/hep.24816
复制
发表时间：
2012-06-01
期刊：
影响因子：
13.5
通讯作者：
Klugewitz, Katja
中科院分区：
文献类型：
--
作者：
Neumann, Katrin;Kruse, Nils;Klugewitz, Katja
肠道激活的T细胞迁移到肝脏可引起炎症性肠病的肠外表现。T细胞获得依赖于由肠树突状细胞（DC）提供的视黄酸（RA）的肠归巢表型。我们研究了肝脏抗原呈递细胞是否能诱导支持肠肝淋巴细胞循环的肠道向性。通过肝窦内皮细胞（LSEC）引发CD 4 + T细胞支持迁移到肠道和肠道相关淋巴组织中。如对于由肠DC引发的T细胞所观察到的，这种肠向性依赖于由LSEC引发的CD 4 + T细胞的α 4 β 7整联蛋白和CC趋化因子受体9（CCR 9）表达。肠道归巢分子的诱导是由RA介导的，RA是一种维生素A的衍生物，大量储存在肝脏内。LSECs表达功能性视网膜色素酶，并可将维生素A转化为RA。相反，缺乏经由RA受体的信号传导阻止了α 4 β 7整联蛋白和CCR 9在LSEC致敏的CD 4 + T细胞上的表达，从而减少了它们向肠的体内迁移。其他肝抗原呈递细胞不能支持α 4 β 7整联蛋白在CD 4 + T细胞上的高表达，因此，诱导肠道归巢的潜力限于LSEC。结论：通过使用维生素A促进肠道向性的能力不是肠道DC所独有的，但也是LSEC的一个特征。我们的数据支持这样的假设，即CD 4 + T细胞可以从肝脏迁移到肠道的一个分支的一个假定的肝肠淋巴细胞循环。（肝脏学2012;55：19761984）
Gut-activated T cells migrating into the liver can cause extraintestinal manifestations of inflammatory bowel disease. T cells acquire a gut-homing phenotype dependent on retinoic acid (RA) provided by intestinal dendritic cells (DC). We investigated whether liver antigen-presenting cells can induce gut tropism supporting an enterohepatic lymphocyte circulation. Priming of CD4+ T cells by liver sinusoidal endothelial cells (LSEC) supported migration into gut and gut-associated lymphoid tissue. As observed for T cells primed by intestinal DCs, this gut tropism depended on a4 beta 7 integrin and CC chemokine receptor 9 (CCR9) expression by LSEC-primed CD4+ T cells. The induction of gut-homing molecules was mediated by RA, a derivate of vitamin A that is stored in large amounts within the liver. LSECs expressed functional retinal dehydrogenases and could convert vitamin A to RA. Conversely, the lack of signaling via the RA receptor prevented the expression of a4 beta 7 integrin and CCR9 on LSEC-primed CD4+ T cells, consequently reducing their in vivo migration to the intestine. Other liver antigen-presenting cells failed to support high expression of a4 beta 7 integrin on CD4+ T cells, thus, the potential to induce gut homing is restricted to LSECs. Conclusion: The capacity to promote gut tropism via vitamin A use is not unique for intestinal DCs but is also a feature of LSECs. Our data support the assumption that CD4+ T cells can migrate from the liver to the gut as one branch of a postulated enterohepatic lymphocyte circulation. (HEPATOLOGY 2012;55:19761984)