The evolution of the immune protein

The evolution of the immune protein.


Scientists at Trinity College Dublin have made a major breakthrough in understanding how inflammation is regulated. They have just discovered a protein with a key role in the immune alarm response. Their work has numerous potential implications, especially in the context of understanding and responding to autoimmune disorders and inflammation. Although our immune system performs an important function of protecting against infection and injury, when immune responses become too aggressive it can lead to harmful inflammation, which occurs in conditions such as rheumatoid arthritis and psoriasis .. Inflammation is triggered when our bodies produce ‘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 advances in the treatment of many immune diseases.


Now, scientists at Trinity College Dublin’s Smurfit Institute of Genetics, led by Smurfit Professor of Genetics, Seamus Martin, have discovered that Interleukin-37 has an unexpected function as an immune activating molecule, as previous studies suggested it this interleukin instead served as an “ off switch ” for the immune system.

Professor Martin said:

“Interleukins play key roles 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 been a major obstacle to understanding what it does, given that much of what we know about the human immune system was first discovered in model organisms whose biological makeup is similar to ours.”


Prior to the new study, Interleukin-37 was thought to have immunosuppressive functions, but exactly how it shuts down inflammation was hotly debated. However, Trinity scientists now report that, when activated in the correct way, they show potent pro-inflammatory activity.


The unexpected role of interleukin-37

“This pro-inflammatory impact was highly unexpected. Our work shows that the protein binds to an interleukin receptor in the skin which is known to play a key role in causing psoriasis. And, to add further intrigue to the story, this bumps up to four the total number of immune alarm molecules signaling through this particular interleukin receptor.

“Why there are so many interleukins binding to the same receptor is a mystery, but if we were to speculate it could be because this receptor performs an important signaling function in our skin and a single alarm protein could simply not be enough to respond to the many different infectious agents our skin encounters. The skin is the main barrier between our body and the outside world that microbes must overcome to enter our bodies and, in many respects, represents the first line of defense of our immune system”. For this reason, Interleukin-37 and other immune alarm proteins may have evolved to become distinct variations on the same theme that allow our bodies to detect different types of activating different enzymes for each infectious agent .



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