Scientists from the San Raffaele Telethon Institute for Gene Therapy (Sr-Tiget) in Milan have discovered the role of a gene that acts as a switch for the production of interferon beta (β), a key molecule to defend the body from viruses such as the Sars-CoV-2 of Covid-19 or from the development of tumors. The research, published in ‘Immunity’ and coordinated by Renato Ostuni, head of the genomics laboratory of the innate immune system at the SR-Tiget, indicates “a new therapeutic target to modulate the immune response”. With “important implications in the fight against infectious and oncological diseases”, underline the authors, according to which the work also opens the way to the development of “more effective gene therapy protocols for rare diseases”.
Type I interferons, which include interferon β – explain Irccs San Raffaele and Fondazione Telethon – are among the most powerful inflammatory molecules. As such, these proteins are essential for our survival, but also potentially dangerous: if in fact they are not produced sufficiently when needed, the immune system cannot successfully defend us against pathogens and tumors; however, if they are produced in excess and out of context, they can favor the onset of autoimmune and inflammatory diseases. “This is why – underlines Ostuni – evolution has produced a redundant series of safety switches: different genes that must be activated in series before allowing the synthesis of interferons. This is a protection system designed to prevent these inflammatory molecules are released into the tissues when it is not strictly necessary “.
Several genes involved in the regulatory processes of interferons have long been discovered, the scholars recall. Now Ostuni and colleagues describe a new one: it is called MEF2A and encodes a protein (a transcription factor) already known for its role in the development of the nervous and muscular systems. Before now, however, no one suspected that MEF2A could also play such an important role in the functioning of the immune system.
Researchers – a note details – arrived at MEF2A by studying the mechanism of action of a molecule, prostaglandin E2 or PGE2, known for its ability to modulate immune responses. Normally, PGE2 prevents interferons from being released when not needed and therefore helps keep tissues healthy. “PGE2 – adds Ostuni – is also an essential ingredient in gene therapy protocols, because it allows the cultivation and engineering of blood stem cells, preserving their full functionality. And international studies suggest that PGE2 can even promote bone marrow regeneration. after the transplant “.
As unfortunately often happens – the researchers point out – cancer cells are able to alter some physiological properties and exploit them to their advantage. Prostaglandin E2 is in fact produced in large quantities in some types of tumors which, in doing so, escape the control of the immune system.
“The downside of having so many control mechanisms for inflammatory molecules such as interferons – points out Ostuni – is that the system is particularly vulnerable to tumor cell ‘hacking’ strategies: just block one of the switches to prevent the release of interferons and keep the immune system at bay “.
The discovery of a new gene that regulates the production of interferon β, and the ability of prostaglandin E2 to limit its function, has “multiple applications – the scientists point out – ranging from the treatment of infectious diseases to the development of new immunotherapy strategies for tumors.
“Not only that: it will also allow us to improve gene therapy protocols – adds Ostuni – The regenerative capacity of blood stem cells is in fact compromised by inflammatory phenomena, both during genetic correction in the laboratory and following transplantation in patients”.
The research group is already working to translate the result of this basic research, conducted through cutting-edge technologies and bioinformatics analysis – the note specifies – into advanced cell therapies, the key mission of SR-Tiget. “Interferon β – concludes Ostuni – is a fundamental molecule in regulating the immune response in many situations: knowing the genes that control its production opens up exciting prospects, which we can’t wait to explore”.