Immune-related GTPase Irgm1 exacerbates experimental auto-immune encephalomyelitis by promoting the disruption of blood-brain barrier and blood-cerebrospinal fluid barrier.
Mol Immunol
; 53(1-2): 43-51, 2013 Jan.
Article
in En
| MEDLINE
| ID: mdl-22796503
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood-Brain Barrier
/
T-Lymphocytes
/
Chemotaxis, Leukocyte
/
GTP-Binding Proteins
/
Encephalomyelitis, Autoimmune, Experimental
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Immunol
Year:
2013
Type:
Article
Affiliation country:
China