Claudin-1 induced sealing of blood–brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis

摘要: In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood-brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into CNS and BBB leakiness. Here we show that sealing TJs by ectopic tetracycline-regulated expression TJ claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on trafficking across during EAE furthermore did not onset severity first clinical disease episode. However, significantly reduce leakiness both blood borne tracers endogenous plasma proteins specifically around vessels expressing claudin-1. addition, exhibited a reduced burden chronic phase as compared to control littermates. Our study identifies critical structure regulating permeability but EAE, indicates dysfunction is potential key event contributing EAE. observations suggest stabilizing function therapeutic targeting may be beneficial treating MS, especially when anti-inflammatory treatments have failed.