Scientists at The Scripps Research Institute (TSRI) have discovered an important process by which special immune cells in the skin help heal wounds. They found that these skin-resident immune cells function as "first responders" to skin injuries in part by producing the molecule known as interleukin-17A (IL-17A), which wards off infection and promotes wound healing.
"This appears to be a critical and unique component of mammals' defense against skin wounds, and we hope that it will point the way towards better therapies for people with difficulties in healing wounds," said TSRI Professor Wendy L. Havran. Havran was senior author of the study, which was published this week online ahead of print by the Journal of Clinical Investigation.
More than Sentinels
Havran and other researchers have shown in recent years that special immune cells known as dendritic epidermal T cells (DETCs) are the only resident T cell population in the outer layer of skin (epidermis) of mice -- and are resident in human skin, too. These cells are now thought to serve as the immune system's principal sentinels in the skin -- when they detect damage signals from nearby wounded skin cells, they summon other, non-skin-resident immune cells to the site of the wound. Skin injuries in mice that have been bred to lack DETCs take much longer than normal to heal.
In the new study, Havran's laboratory looked for new ways in which DETCs contribute to wound healing.
In one set of experiments, Senior Research Associate Amanda S. MacLeod, the lead author of the study, and other members of the team tried to determine whether DETCs in mice produce IL-17A in response to skin wounding. IL-17A had been considered mainly a recruiter of other immune cells and thus a promoter of inflammation in most places in the body. Havran and her colleagues had found evidence that it appears in and around skin wounds in mice soon after an injury occurs.
The scientists soon determined that mice that lack IL-17A activity healed wounds on their skin much more slowly than normal -- very much like mice that lack DETCs. Applying IL-17A to the skin of such mice repaired their wound-healing defects. The team then showed that the rise in local IL-17A levels after a skin wound depended critically on the activation of skin-resident DETCs -- pointing to these DETCs as the likely source of the immune signaling molecule. In the mice that lack IL-17A, adding normal DETCs from other mice fully restored a healthy wound-healing capacity and did so only when the added DETCs contained the gene that allows these cells to produce IL-17A.
The scientists found that DETCs are indeed the primary producers of IL-17A after skin injuries, but she observed that some and not all DETCs perform this function. "Only a subset produces IL-17A upon skin injury, although the surface markers on these cells seem identical to those of other DETCs," MacLeod said. "Why only some DETCs respond to wounds in this way is something we plan to explore further."