Human Factors and Behavioral Neurobiology
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.
Grant or Award Name
Canadian Institutes of Health Research grants MOP-15291, MOP-15415, PS-153325, MOP-15291, MOP-86750, and PS-153325. A generous donation from Kenneth McCourt family. The Multiple Sclerosis Society of Canada (EGID2426. The Royal Devon and Exeter Hospital Foundation Trust and Northcott Devon Medical Foundation. A generous donation from Sheryl Moorey’s family. The Alberta Innovates-Health Solutions (AI-HS) studentship. The Multiple Sclerosis Society of Canada studentship. The AI-HS postdoctoral fellowship. The Alberta MS Network summer studentship award.
Scholarly Commons Citation
Paul, A. M., Jung, J., Eggleton, P., Robinson, A., Wang, J., & Gutowski, N. (2018). Calnexin Is Necessary for T Cell Transmigration into the Central Nervous System. JCI Insight, 3(5). https://doi.org/10.1172/jci.insight.98410
Behavioral Neurobiology Commons, Immune System Diseases Commons, Immunity Commons, Molecular and Cellular Neuroscience Commons, Neurology Commons
Dr. Paul was not affiliated with Embry-Riddle Aeronautical University at the time this paper was published.