New research from Rockefeller’s Elaine Fuchs’ lab and published in Cell has identified a protective mechanism in the skin that responds to injury signals in wounded tissue. This new pathway responds to low oxygen levels from blood vessel disruption and scab formation, and does not require an infection to get into gear. These findings represent the first identification of a damage response pathway that is distinct from the classical pathway triggered by pathogens.
At the center of this pathway is interleukin-24 (IL24), a secreted protein that initiates various cellular strategies to begin the complex healing process. When activated, the IL24 signal coordinates the repair of different tissue types in a coordinated way, including the replacement of damaged epithelial cells, healing of broken capillaries, and generation of fibroblasts for new skin cells.
While researchers have understood how host responses protect the body from pathogen-induced threats, this new pathway sheds light on how the body responds to an injury that may or may not involve a foreign invader. IL24’s role in this new injury response pathway is significant, as researchers have found that without it, the healing process is sluggish and delayed.
The team speculates that IL24 might be involved in the injury response in other body organs featuring epithelial layers, which act as a protective sheath. They found that elevated IL24 activity has been spotted in epithelial lung tissue of patients with severe COVID-19 and colonic tissue in patients with ulcerative colitis, a chronic inflammatory bowel disease.
Interestingly, evolutionary analysis revealed that IL24 and its receptors share close sequence and structure homology with the interferon family. Although they may not always work in tandem at every moment, IL24 and interferons are evolutionarily related and bind to receptors sitting near each other on the surface of cells. The researchers speculate that these signaling molecules derive from a common molecular pathway dating far back in our past and hope this discovery will inspire new approaches to promote tissue repair and regeneration.