CD99L2 deficiency inhibits leukocyte entry into the central nervous system and ameliorates neuroinflammation
CD99L2 deficiency inhibits leukocyte entry into the central nervous system and ameliorates neuroinflammation
复制标题
DOI：
10.1002/jlb.1a0617-228r
复制
发表时间：
2018-10-01
影响因子：
5.5
通讯作者：
Vestweber, Dietmar
中科院分区：
文献类型：
--
作者：
Samus, Maryna;Seelige, Ruth;Vestweber, Dietmar
白细胞进入中枢神经系统是多发性硬化及其实验性自身免疫性脑脊髓炎（EAE）动物模型发展的关键步骤。介导白细胞与血脑屏障（BBB）内皮对接的粘附分子是干预该疾病的有价值的靶点。然而，很少有人知道的粘附和信号转导机制，在内皮细胞介导的血透通过血脑屏障。在此，我们表明条件性Tie-2-Cre驱动的CD 99 L2基因失活在活性MOG（35-55）诱导的EAE期间抑制白细胞进入CNS，并减轻疾病的严重程度。未观察到对免疫应答的有害影响。CNS血管周围血管袖的数量减少，炎性病灶的数量、脱髓鞘部位和促炎细胞因子的表达水平也减少。CNS的振动切片的三维分析揭示了白细胞在内皮细胞和下面的基底膜之间的积累，而白细胞对接到BBB的内皮的管腔表面不受影响。总的来说，这些结果表明，CD 99 L2通过支持白细胞通过CNS中BBB血管的内皮基底膜渗出而参与EAE的发展。
Leukocyte entry into the CNS is a crucial step in the development of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Adhesion molecules mediating the docking of leukocytes to the endothelium of the blood-brain barrier (BBB) represent valuable targets for interference with the disease. However, little is known about the adhesion and signaling mechanisms in endothelial cells that mediate the diapedesis through the BBB. Here, we show that conditional Tie-2-Cre driven gene inactivation of CD99L2 inhibits leukocyte entry into the CNS during active MOG(35-55)-induced EAE and alleviates severity of the disease. No detrimental effect on the immune response was observed. The number of perivascular cuffs around vessels of the CNS was reduced, as was the number of inflammatory foci, sites of demyelination and expression levels of pro-inflammatory cytokines. Three-dimensional analysis of vibratome sections of the CNS revealed an accumulation of leukocytes between endothelial cells and the underlying basement membrane, whereas leukocyte docking to the luminal surface of the endothelium of the BBB was unaffected. Collectively, these results suggest that CD99L2 participates in the development of EAE by supporting diapedesis of leukocytes through the endothelial basement membrane of blood vessels of the BBB in the CNS.