神经炎症
实验性自身免疫性脑脊髓炎
血管生成素受体
促炎细胞因子
免疫学
小胶质细胞
医学
血脑屏障
炎症
中枢神经系统
癌症研究
内分泌学
血管生成
作者
Zhilin Li,Emilia A. Korhonen,Arianna Merlini,Johannes Strauß,Eleonoora Wihuri,Harri Nurmi,Salli Antila,Jennifer Paech,Urban Deutsch,Britta Engelhardt,Sudhakar Chintharlapalli,Gou Young Koh,Alexander Flügel,Kari Alitalo
摘要
Angiopoietin-2 (Ang2), a ligand of the endothelial Tie2 tyrosine kinase, is involved in vascular inflammation and leakage in critically ill patients. However, the role of Ang2 in demyelinating central nervous system (CNS) autoimmune diseases is unknown. Here, we report that Ang2 is critically involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis. Ang2 expression was induced in CNS autoimmunity, and transgenic mice overexpressing Ang2 specifically in endothelial cells (ECs) developed a significantly more severe EAE. In contrast, treatment with Ang2-blocking Abs ameliorated neuroinflammation and decreased spinal cord demyelination and leukocyte infiltration into the CNS. Similarly, Ang2-binding and Tie2-activating Ab attenuated the development of CNS autoimmune disease. Ang2 blockade inhibited expression of EC adhesion molecules, improved blood-brain barrier integrity, and decreased expression of genes involved in antigen presentation and proinflammatory responses of microglia and macrophages, which was accompanied by inhibition of α5β1 integrin activation in microglia. Taken together, our data suggest that Ang2 provides a target for increasing Tie2 activation in ECs and inhibiting proinflammatory polarization of CNS myeloid cells via α5β1 integrin in neuroinflammation. Thus, Ang2 targeting may serve as a therapeutic option for the treatment of CNS autoimmune disease.
科研通智能强力驱动
Strongly Powered by AbleSci AI