Small infections can be fatal: millions of people die each year from sepsis, an overreaction of the immune system. A new immune signalling molecule, designed by a research team from the Technical University of Munich (TUM), now provides the basis for potential new approaches in sepsis therapy.
Researchers around the world have long been searching for new therapies. An interdisciplinary team from the fields of structural biology, immunology and cell biology has now, for the first time, successfully produced a protein that could balance the overshooting immune response.
In their work, the scientists were inspired by evolution: mice are well protected from sepsis by their immune systems. Here, interleukins – messengers that mediate communication between the cells of the immune system – play a key role.
“The interleukins are the vocabulary with which immune cells communicate,” explains Matthias Feige, professor of Cellular Protein Biochemistry at the TUM. The cells form these messenger molecules according to a very specific blueprint of individual amino acids. Their arrangement determines which three-dimensional structure an interleukin adopts and, consequently, which information it transmits.
Humans and mice have similar, yet different vocabularies. The researchers discovered one striking difference in interleukin-27-alpha. This molecule can be released by cells of the mouse immune system but not by human cells and regulates immune cell function.
“Using computer models and cell biological experiments, we discovered that a single structurally important amino acid defines whether interleukin-27-alpha is released by cells of the immune system,” explains Stephanie Müller, the first author of the study. “That gave us an idea about how we can engineer novel human interleukin proteins that are released by cells so that we can produce them biotechnologically.”
The team then prepared the modified interleukin in the lab and tested its biological functions – with very encouraging results: the engineered messenger molecule is recognised by human cells. First analyses suggest that it can indeed balance an overreaction of the immune system, making it a promising candidate for sepsis therapy.
