Relapsing-remitting multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is defined by extensive neuronal demyelination and enhanced blood brain barrier (BBB) permeability.
There is a strong sex bias in MS patients, with 3 to 4 female patients for every affected male.
The female bias is recapitulated in SLJ mice with experimental autoimmune encephalitis (EAE), a commonly used MS model.
In this issue of the Journal of Clinical Investigation, Robyn Klein and colleagues at Washington University performed whole transcriptome analysis of transcripts collected from EAE-susceptible CNS regions in naïve SJL mice and determined that female SJL mice express dramatically higher levels of the sphingosine-1 phosphate receptor S1PR2 compared to male animals.
Expression and activity of S1PR2 were associated with endothelial barrier dysfunction, which enhanced BBB permeability and the loss of immune privilege.
Pharmacological inactivation of S1PR2 signaling attenuated BBB permeability and EAE severity. Importantly, female MS patients also exhibited increased expression of S1PR2 in the CNS vasculature during periods of MS-associated CNS autoimmunity, indicating that S1PR2 may be a suitable therapeutic target in humans.