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

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

Department of Neurology, The Affiliated Sanming First Hospital of Fujian Medical University, Sanming 365000, Fujian, China. cdongwang@yahoo.com

Molecular immunology 2013 Jan

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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 naïve 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

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. Immune-related GTPase Irgm1 exacerbates experimental auto-immune encephalomyelitis by promoting the disruption of blood-brain barrier and blood-cerebrospinal fluid barrier. Molecular immunology. 2013 Jan;53(1-2):43-51