AUTHOR=Manchinu Maria Francesca , Simbula Michela , Caria Cristian Antonio , Musu Ester , Perseu Lucia , Porcu Susanna , Steri Maristella , Poddie Daniela , Frau Jessica , Cocco Eleonora , Manunza Laura , Barella Susanna , Ristaldi Maria Serafina 

TITLE=Delta-Globin Gene Expression Is Enhanced in vivo by Interferon Type I

JOURNAL=Frontiers in Medicine

VOLUME=7

YEAR=2020

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.00163

DOI=10.3389/fmed.2020.00163

ISSN=2296-858X

ABSTRACT=<p>Beta hemoglobinopathies are widely spread monogenic lethal diseases. <italic>Delta-globin</italic> gene activation has been proposed as a possible approach for curing these pathologies. The therapeutic potential of delta-globin, the non-alpha component of Hemoglobin A<sub>2</sub> (α2δ2; HbA2), has been demonstrated in a mouse model of beta thalassemia, while its anti-sickling effect, comparable to that of gamma globin, was established some time ago. Here we show that the <italic>delta-globin</italic> mRNA level is considerably increased in a <italic>Deoxyribonuclease II-alpha</italic> knockout mouse model in which type 1 interferon (interferon beta, IFNb) is activated. IFNb activation in the fetal liver improves the <italic>delta-globin</italic> mRNA level, while the <italic>beta-globin</italic> mRNA level is significantly reduced. In addition, we show that HbA2 is significantly increased in patients with multiple sclerosis under type 1 interferon treatment. Our results represent a proof of principle that delta-globin expression can be enhanced through the use of molecules. This observation is potentially interesting in view of a pharmacological approach able to increase the HbA2 level.</p>