Immune-related GTPase Irgm1 exacerbates experimental auto-immune encephalomyelitis by promoting the disruption of blood-brain barrier and blood-cerebrospinal fluid barrier

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• 作者：Chaodong Wang ; Caihong Wang ; Haiyan Dong ; Xiao-Mu Wu ; Chunyu Wang ; Fucan Xia ; Guimei Li ; Xiuzhi Jia ; Shuyu He ; Xiaoshu Jiang ; Huashun Li ; Hongwei Xu
• 关键词：Irgm1 ; EAE ; Blood&ndash ; brain barrier ; Blood&ndash ; cerebrospinal fluid barrier
• 刊名：Molecular Immunology
• 出版年：2013
• 出版时间：January-February, 2013
• 年：2013
• 卷：53
• 期：1-2
• 页码：43-51
• 全文大小：2195 K

文摘

Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), is a T cell-mediated autoimmune condition characterized by prominent inflammation in the CNS. In this model, autoreactive T cells are primed in peripheral lymph nodes and migrate into uninflamed CNS across blood-cerebrospinal fluid barrier (BCSFB) and blood-brain barrier (BBB) to initiate inflammation. However, the molecular mechanism controlling T cell migration remains to be determined. In an in vivo EAE mouse model, we have shown that Irgm1 (also known as LRG-47), a member of the immunity-related GTPase family, promotes the disruption of both BCSFB and BBB, and exacerbates the phenotypes of MOG-induced EAE. During EAE, Irgm1 was up-regulated in reactive astrocytes, ependymal cells and epithelial cells of the choroids plexus, which, in turn, promotes T cell infiltration into the CNS. Electron microscopy study showed that the MOG-induced disruption of both BBB and BCSFB was protected in the Irgm1^?/? mice. Moreover, the expression of Claudin-5 (CLN-5), a major molecular determinant of BBB, in brain microvessel endothelial cells (BMVECs) was decreased in WT EAE mice while increased in Irgm1^?/? mice. In addition, the expression of CC-chemokine ligand 20 (CCL-20), an important chemokine mediating lymphocyte trafficking across BCSFB, in the epithelial cells of choroids plexus was significantly suppressed in na?ve and EAE-induced Irgm1^?/? mice. These data suggest that Irgm1 is an important molecular regulator for the properties of both BBB and BCSFB, and a proinflammatory factor for EAE.