IFN‐β regulates CD73 and adenosine expression at the blood–brain barrier

Abstract IFN‐β treatment reduces the relapse rate in MS but its mechanism of action remains incompletely understood. Our aim was to clarify the beneficial effect of IFN‐β in the treatment of MS. We assessed the influence of IFN‐β treatment on (i) CD73 expression on the surface of primary cultures of human blood–brain barrier endothelial cells (BBB‐EC) and human astrocytes using immunofluorescence staining and flow cytometry, (ii) transmigration of CD4 + T lymphocytes using an in vitro model of BBB and (iii) CD73 enzyme activity, i.e. ecto‐5′‐nucleotidase activity in the serum of MS patients using a radiochemical assay. IFN‐β increases the expression of ecto‐5′‐nucleotidase both on BBB‐EC and astrocytes. As a consequence, lymphocyte transmigration through BBB‐EC is reduced. Importantly, this reduction can be reversed using α,β‐methyleneadenosine‐5′‐diphosphate, a specific inhibitor of ecto‐5′‐nucleotidase. CD73 is strongly expressed in microvasculature in samples of postmortem MS brain and, moreover, in the majority of MS patients there was a clear upregulation both in the soluble serum ecto‐5′‐nucleotidase activity and skin microvascular CD73 expression after IFN‐β treatment. Upregulation of ecto‐5′‐nucleotidase and a subsequent increase in adenosine production might contribute to the beneficial effects of IFN‐β on MS via enhancing the endothelial barrier function.