Immunohistochemical detection of sphingosine-1-phosphate receptor 1 and 5 in human multiple sclerosis lesions

Aims: Sphingosine-1-phosphate receptor (S1PR) modulating therapies are currently in the clinic or undergoing investigation for multiple sclerosis (MS) treatment. However, the expression of S1PRs is still unclear in the central nervous system under normal conditions and during neuroinflammation. Methods: Using immunohistochemistry we examined tissues from both grey and white matter MS lesions for sphingosine-1-phosphate receptor 1 (S1P(1)) and 5 (S1P(5)) expression. Tissues from Alzheimer's disease (AD) cases were also examined. Results: S1P(1) expression was restricted to astrocytes and endothelial cells in control tissues and a decrease in endothelial cell expression was found in white matter MS lesions. In grey matter MS lesions, astrocyte expression was lost in active lesions, while in quiescent lesions it was restored to normal expression levels. CNPase colocalization studies demonstrated S1P(5) expression on myelin and both were reduced in demyelinated lesions. In AD tissues we found no difference in S1P(1) expression. Conclusion: These data demonstrate a differential modulation of S1PRs in MS lesions, which may have an impact on S1PR-directed therapies.