Researchers from Japan have discovered the role of interleukin-36 receptor antagonists in healing skin wounds from ischaemia-reperfusion injuries.
Ischaemia is a medical condition in which the blood supply is cut off to different parts of the body. In patients who are bed-ridden, ischemia can manifest as pressure ulcers. Else, it could be the Raynaud’s phenomenon in someone under severe stress. Ischaemia, from the Latin “staunching of blood”, is a condition can be rescued by blood reperfusion to the affected areas. However, ischaemia-reperfusion (I/R) injuries where tissue damage caused by blood returning to tissues after a period of oxygen deprivation, are a risk.
Skin-based I/R injuries can be exacerbated by inherited immunological mechanisms, for instance in patients who are otherwise showing signs of slow wound healing. To understand the immunological mechanisms underlying the development of this condition better, decided to narrow down their investigation to interleukin-36 receptor antagonist (IL-36Ra), a protein that plays a pivotal immunomodulatory role in wound healing.
Lead researcher Mr Yoshihito Tanaka from Fujita Health University School of Medicine explained the motivation behind the research, “We wanted to understand the immunological mechanisms involved in the healing of wounds from cutaneous ischaemia-reperfusion injuries, such as pressure ulcers and Raynaud’s phenomenon, to narrow down possible therapeutic targets. Drawing from experience, IL-36Ra appeared to be a promising candidate for kickstarting our investigation.”
The scientists used mice knocked out for the IL-36Ra receptor, and induced cutaneous I/R injuries in the knockout and control mice. Then, they studied corresponding immunological responses in both groups of animals, including wound healing time, infiltration of neutrophils/macrophages to the site of the wounds, apoptotic skin cells, and activation of other unwanted immunological defense mechanisms. Their findings appear in the Journal of The European Academy of Dermatology and Venereology.
They found that the absence of IL-36Ra, indeed, significantly slows down wound healing in cutaneous I/R injuries, through increased apoptosis, or ‘suicide’ of useful skins cells, excessive recruitment of inflammatory cells, and employment of unnecessary proinflammatory mechanisms.
Additionally, they demonstrated the role of Cl-amidine, a protein-arginine deiminase inhibitor as effective in normalizing exacerbated I/R injury in IL-36Ra mice. Based on these observations, the scientists assert their findings are the first conclusive report of the involvement of IL-36Ra in cutaneous I/R injury.
The researchers believe IL-36Ra is a good therapeutic candidate against cutaneous I/R injuries. As Mr. Tanaka optimistically adds, “Our research may lead to the development of therapeutic agents for wound healing of various other refractory skin diseases too.”
The quest for novel therapeutic targets in skin wound healing might just have been empowered by these findings of the team and the future indeed looks brighter for alleviating the painful burden of cutaneous I/R injuries.
