New study aims to understand why skin grafts have a high rejection rate

With regard to transplant rejection, some organs are much more delicate than others. Some transplantable organs, such as the liver, are easily accepted by the recipient's immune system, rarely triggering an immune response and rejection. But the skin is very different: skin grafts have a high rejection rate for unknown reasons.

Researchers at Brigham and Women's Hospital have sought to understand why, hoping to take advantage of new biological knowledge to explain not only why skin grafts cause the immune system, but also what treatments can be administered to an organ before transplantation to reduce the risk of rejection. Their results, with implications for the future of facial transplantation, are published in Nature Communications.

"Our laboratory work is guided by clinical observation," said lead co-author Leonardo V. Riella, MD, PhD, medical director of the vascularized composite tissue transplant program at BWH. "Skin grafts have such a high rejection rate compared to other organs, we wanted to know why."

Using a mouse model of skin transplantation, the team identified a new specific subset of cells in organs transplanted by donors that triggered a rejection. Known as CD103 + dendritic cells, this type of cell appears to play a major role in rejection. In his absence, the researchers observed fewer signs indicating that the recipient's immune system had been triggered and found that the transplanted skin had survived longer.

In addition, the team was able to mitigate the rejection by treating the organs before transplantation. When skin grafts were incubated with an anti-inflammatory mycobacterial protein, the grafts survived longer after transplantation. This effect was mediated by March-1, an enzyme that can inhibit the maturation of CD103 + dendritic cells in donor grafts. In addition to these observations in murine models, the team also tested the effect of adding mycobacterial protein to human skin grafts, finding signs that this treatment could help prevent an immune response.

Pretreatment of skin grafts or other organs prior to transplantation represents a new complementary strategy to prevent organ rejection. "Today, most treatments focus on the recipient side, using immunosuppressive drugs to try to prevent rejection," Riella said. "What we are proposing is a complementary strategy to tame the rejection process through direct treatment of the donor organ prior to transplantation.This could offer many benefits since we are focusing on one arm of the immune system – the Innate immunity – "

The researchers plan to continue to test the safety and effectiveness of this strategy in preclinical models and, if successful, will conduct Phase 1 clinical trials in humans in the coming years. .