کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2831133 | 1570729 | 2013 | 9 صفحه PDF | دانلود رایگان |
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.
► Irgm1 was up-regulated in brain and spinal cord during EAE.
► Irgm1 promotes T cell infiltration into the CNS.
► Irgm1 promotes the disruption of both blood–brain barrier and brain–CSF barrier in CNS.
► The expression of Claudin-5 was decreased in wild-type EAE mice while increased in Irgm1 KO mice.
► The expression of CC-chemokine ligand 20 was suppressed in Irgm1 KO mice.
Journal: Molecular Immunology - Volume 53, Issues 1–2, January–February 2013, Pages 43–51