Related Experiment Video
Updated: Jun 29, 2026
Paired Cisterna Magna Nanoinjection and Laser Speckle Contrast Imaging Assay to Study Cerebral Blood Flow Regulation In Vivo
Published on: July 8, 2025
IFN-beta regulates CD73 and adenosine expression at the blood-brain barrier
Jussi Niemelä1, Igal Ifergan, Gennady G Yegutkin
1Department of Medical Microbiology, MediCity Research Laboratory, University of Turku, Turku, Finland.
Abstract:
IFN-beta 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-beta in the treatment of MS. We assessed the influence of IFN-beta 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-beta 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 alpha,beta-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-beta treatment. Upregulation of ecto-5'-nucleotidase and a subsequent increase in adenosine production might contribute to the beneficial effects of IFN-beta on MS via enhancing the endothelial barrier function.
Insights
Interferon-beta (IFN-beta) enhances CD73 expression on the blood-brain barrier, reducing T cell infiltration in multiple sclerosis (MS). This mechanism may explain IFN-beta
Area of Science:
- Neuroimmunology
- Cellular and Molecular Biology
- Biochemistry
Background:
- Interferon-beta (IFN-beta) is a treatment for multiple sclerosis (MS) that reduces relapse rates.
- The precise mechanism by which IFN-beta exerts its beneficial effects in MS is not fully understood.
- Understanding the molecular pathways involved is crucial for optimizing MS treatment strategies.
Purpose of the Study:
- To elucidate the mechanism of action of IFN-beta in treating MS.
- To investigate the impact of IFN-beta on CD73 expression and activity.
- To assess the effect of IFN-beta on T lymphocyte transmigration across the blood-brain barrier (BBB).
Main Methods:
- Immunofluorescence staining and flow cytometry to quantify CD73 expression on human brain microvascular endothelial cells (HBMECs) and astrocytes.
- In vitro model of the BBB to assess CD4+ T lymphocyte transmigration.
- Radiochemical assay to measure serum ecto-5'-nucleotidase (CD73) activity in MS patients.
- Pharmacological inhibition of CD73 using alpha,beta-methyleneadenosine-5'-diphosphate.
Main Results:
- IFN-beta treatment significantly increased CD73 expression on HBMECs and astrocytes.
- IFN-beta treatment reduced CD4+ T lymphocyte transmigration across the in vitro BBB model.
- This reduction in transmigration was reversible with a specific CD73 inhibitor.
- MS patients showed upregulated soluble CD73 activity and microvascular CD73 expression post-IFN-beta treatment.
- CD73 was highly expressed in MS brain microvasculature.
Conclusions:
- IFN-beta upregulates CD73 expression and activity on the blood-brain barrier.
- Increased CD73 expression enhances endothelial barrier function by reducing T lymphocyte infiltration.
- This CD73-mediated mechanism contributes to the therapeutic benefits of IFN-beta in MS.
- Adenosine production, facilitated by CD73, may play a key role in IFN-beta's efficacy.
More Related Videos
10:24Simultaneous Flow Cytometric Characterization of Multiple Cell Types Retrieved from Mouse Brain/Spinal Cord Through Different Homogenization Methods
Published on: November 19, 2019
06:19Reconstruction of the Blood-Brain Barrier In Vitro to Model and Therapeutically Target Neurological Disease
Published on: October 20, 2023
Related Concept Videos
00:49The Blood-brain Barrier
01:26Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...