Scientists have discovered how a key immune alarm protein previously believed to calm down the immune response actually does the opposite. Their work has numerous potential impacts, especially in the context of understanding and responding to autoimmune disorders and inflammation.
‘The interleukin-37 binds to an interleukin receptor in the skin that is known to play a key role in driving psoriasis.’
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While our immune system serves a very important function protecting us from infection and injury, when immune responses become too aggressive this can lead to damaging inflammation, which occurs in conditions such as rheumatoid arthritis and psoriasis. Inflammation is triggered when our bodies produce “alarm proteins” (interleukins), which ramp up our defences against infection and injury by switching on different components of our immune system. Understanding how and when such alarm proteins are produced and how they activate our immune system has led to major breakthroughs in the treatment of many immune conditions.
Interleukin-37: The Effect of Anti-Inflammatory Response in Human
Now, scientists from the Smurfit Institute of Genetics at Trinity College Dublin, led by Seamus Martin, Smurfit Professor of Genetics, have found that interleukin-37 has an unexpected function as an immune-activating molecule, as previous studies suggested that this interleukin instead served as an ‘off switch’ for the immune system.Professor Martin said:
“Interleukins play key roles in regulating our immune systems in response to bacterial and fungal infections. However, Interleukin-37 has long remained an enigma, as it isn’t found in mammals such as mice. This has presented a major obstacle to figuring out what it does as much of what we know about the human immune system has first been discovered in model organisms whose biological make-ups are similar to ours.”
Prior to the new study, Interleukin-37 was thought to have immune-suppressive functions but how exactly it switched off inflammation was hotly debated. However, the Trinity scientists now report that, when activated in the correct way, Interleukin-37 displays potent pro-inflammatory activity.
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“This pro-inflammatory impact was highly unexpected. 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.”
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As such, interleukin-37 and other immune alarm proteins may have evolved to become distinct variations on the same theme that enable our bodies to detect different types of infection by becoming activated by enzymes that are distinct to each infectious agent.
The research has just been published in the internationally renowned journal, Science Immunology, and was collaboration between several Trinity research groups led by Professor Martin's team, which included post-doctoral scientists Dr. Graeme Sullivan and Dr. Pavel Davidovich, along with research groups led by Professor Ed Lavelle (School of Biochemistry and Immunology) and Professor Pat Walsh (School of Clinical Medicine).
Source-Eurekalert