Science Immunology reveals the true face of this protein: evolutionary alarm molecules that drive inflammation

Scientists at Trinity College Dublin have made an important breakthrough
in understanding how inflammation is regulated.
They have just discovered that a key immune alarm protein previously thought to calm immune responses actually plays the opposite role
.

Their work has many potential implications, particularly in
understanding and responding to autoimmune diseases and inflammation.

While our immune system plays a very important role in protecting us from infection and injury, when the immune response becomes too intense, it can lead to damaging inflammation such as rheumatoid arthritis and psoriasis
.
Inflammation is triggered when our body produces "alarm proteins" (interleukins), which strengthen our defenses against infection and injury by activating different components of the 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 at Trinity College Dublin's Smurfit Institute of Genetics, led by Smurfit Professor of Genetics Seamus Martin, have discovered that interleukin-37 has unexpected functions as an immune-activating molecule, as previous studies have shown that this interleukin, instead acts as an "off switch"
for the immune system.

Professor Martin said:

"Interleukin plays a key role
in regulating our immune system to respond to bacterial and fungal infections.
However, interleukin-37 has long been a mystery because it has not been found
in mammals such as mice.
This presents a major hurdle in figuring out what it does, as much of what we know about the human immune system was first discovered in model organisms with biological
compositions similar to ours.
”

Prior to the new study, interleukin-37 was thought to have immunosuppressive functions, but exactly how it eliminates inflammation is hotly debated
.
However, scientists at Trinity College now report that interleukin-37 shows powerful pro-inflammatory activity
when activated in the right way.

Professor Martin added:

"This pro-inflammatory effect is very unexpected
.
Our study shows that this protein binds to interleukin receptors in the skin, which are known to play a key role
in triggering psoriasis.
And, to make this story even more interesting, this brings the total number of immune alarm molecules signaled through this particular interleukin receptor to four
.

"Why so many interleukins bind to the same receptor is a mystery, but if we speculate that it may be because this receptor plays a very important sentinel function in our skin, one alert protein may not be enough to deal with the many different infectious agents
our skin encounters.
" Our skin is the main barrier between our bodies and the outside world, having to break through if microbes are to enter our bodies, and in many ways, it represents the first line
of defense of our immune system.
”

Thus, interleukin-37 and other immune alert proteins may have evolved into different variants of the same topic, allowing our bodies to detect different types of infections
by being activated by enzymes different for each infectious agent.