Scientists at Trinity College Dublin have made a major breakthrough in understanding the regulation of inflammation. They have just discovered that a key immune alarm protein previously thought to calm the immune response actually does the opposite.
Their work has many potential impacts, particularly in the context of understanding and responding to autoimmune diseases and inflammation.
Although our immune system performs a very important function in protecting us from infection and injury, when immune responses become too aggressive it can lead to damaging inflammation, which occurs in conditions such as rheumatoid arthritis and psoriasis. Inflammation is triggered when our body produces “alarm proteins” (interleukins), which boost our defenses against infection and injury by activating different components of our immune system.
Understanding how and when these alarm proteins are produced and how they activate our immune system has led to major breakthroughs in the treatment of many immune diseases.
Now scientists from the Smurfit Institute of Genetics at Trinity College Dublin, led by Seamus Martin, Smurfit Professor of Genetics, have discovered that interleukin-37 has an unexpected function as an immune activating molecule, as previous studies suggested that this interleukin served more as an “off switch” for the immune system.
Professor Martin said:
“Interleukins play a key role in regulating our immune system in response to bacterial and fungal infections. However, interleukin-37 has long remained an enigma, as it is not found in mammals such as mice. This has presented a major hurdle to understanding what it does, much of what we know about the human immune system was first discovered in model organisms whose biological makeup is similar to our own. »
Prior to the new study, interleukin-37 was thought to have immunosuppressive functions, but exactly how it quenches inflammation has been hotly debated. However, Trinity scientists now report that when activated in the right way, interleukin-37 displays potent pro-inflammatory activity.
Professor Martin added:
“This pro-inflammatory impact was very unexpected. Our work shows that the protein binds to an interleukin receptor in the skin which is known to play a key role in driving psoriasis. And, to add further intrigue to the story, this brings the total number of immune alarm molecules that signal via this particular interleukin receptor to four.
“Why there are so many interleukins that bind to the same receptor is a mystery, but if we had to speculate, it may be because this receptor performs a very important sentinel function in our skin, and a protein of alarm may simply not be enough to respond to the many different infectious agents that our skin encounters. Our skin is the main barrier between our body and the outside world that germs must cross if they want to enter our body and, in many ways, represents the first line of defense in our immune system. »
As such, interleukin-37 and other immune alarm proteins may have evolved into distinct variations on the same theme that allow our bodies to detect different types of infection by becoming activated by distinct enzymes. for each infectious agent.
The research has just been published in the internationally renowned journal, Sciences Immunologie, and was a collaboration between several Trinity research groups led by Professor Martin’s team, which included postdoctoral scientists Dr Graeme Sullivan and Dr Pavel Davidovich, as well as research groups led by Professor Ed Lavelle (School of Biochemistry and Immunology) and Professor Pat Walsh (School of Clinical Medicine).