期刊
JCI INSIGHT
卷 3, 期 5, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.98410
关键词
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资金
- Multiple Sclerosis Society of Great Britain and Northern Ireland [207495]
- Canadian Institutes of Health Research [MOP-15291, MOP-15415, PS-153325, MOP-86750, PS-53325]
- Kenneth McCourt family
- Multiple Sclerosis Society of Canada [EGID2426]
- Royal Devon and Exeter Hospital Foundation Trust
- Northcott Devon Medical Foundation
- Sheryl Moorey's family
- Alberta Innovates-Health Solutions (AI-HS) studentship
- AI-HS postdoctoral fellowship
- Alberta MS Network summer studentship award
In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS. Furthermore, calnexin deficiency in mice did not alter the development or function of the immune system. Instead, the loss of calnexin led to a defect in brain endothelial cell function that resulted in reduced T cell trafficking across the blood-brain barrier. These findings identify calnexin in brain endothelial cells as a potentially novel target for developing strategies aimed at managing or preventing the pathogenic cascade that drives neuroinflammation and destruction of the myelin sheath in MS.
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