The immune system serves a very important function, but it can lead to destructive inflammation with the production of “alarm proteins” (interleukins), which strengthen the defense by activating different elements of our immune system.

Researchers discovered that IL-37 has an unexpected function as an immune-activating molecule, as previous studies suggested IL-37 served.

as an “off switch” for the immune system. For IL-37 [IL-1 family] work has shown that it suppresses the production of inflammatory cytokines. IL-37 is activated by caspase-1 and exerts anti-inflammatory activity through binding to IL-18R [IL-37 and IL-36 share structural homology].

However, it has recently been revealed that it can be cleaved by elastase and cathepsin of neutrophils to generate an active form that exhibits unexpected potent proinflammatory activity in keratinocytes.

The work shows that the protein binds to an interleukin receptor in the skin known to play a key role in psoriasis.

In the new study the scientists now report that IL-37 exhibits an unexpectedly strong pro-inflammatory effect.

Why there are so many interleukins that bind to the same receptor [IL-36R] may be because it serves an important sentinel function in the skin that represents the first line of defense in the immune system.

Therefore, IL-37 [like other immune signaling proteins] may have evolved so that the body detects different types of infection and activates different enzymes for each infectious agent.

SOURCE: Science Immunology Dec.2022