Modified Mice Less Susceptible to Multiple Sclerosis
Have reduced migration of lymphocytes into central nervous system
WEDNESDAY, July 2 (HealthDay News) -- Mice lacking a certain protein are less susceptible to developing a form of multiple sclerosis due to reduced migration of lymphocytes into the central nervous system, according to the results of a study published in the July 8 issue of the Proceedings of the National Academy of Sciences.
Jeffrey H. Mills, from Cornell University in Ithaca, N.Y., and colleagues examined the susceptibility of mice lacking the cd73 gene to develop severe experimental autoimmune encephalomyelitis (EAE). CD73 is a cell surface enzyme that catalyzes the breakdown of AMP to adenosine, an anti-inflammatory and immunosuppressant, they note.
The researchers found that the mice were surprisingly resistant to developing EAE. Their CD4+ T-cell function was normal, they had fewer infiltrating lymphocytes into the central nervous system, and transferring normal CD4+ T cells into the mice could induce EAE. In normal mice, CD73 was not expressed on brain endothelial cells but was highly expressed in the choroid plexus epithelium, which regulates immunosurveillance of lymphocytes between the brain and cerebrospinal fluid, the investigators report. Blocking adenosine signaling in normal mice by blocking an adenosine receptor with a drug protected them from developing EAE.
"Our work demonstrates a requirement for CD73 expression and adenosine receptor signaling for the efficient entry of lymphocytes into the central nervous system during EAE," Mills and colleagues conclude. "The data presented here may mark the first steps of a journey that will lead to new therapies for multiple sclerosis and other neuroinflammatory diseases."