Role Identified for Complement Receptor in Heart Transplant Rejection

Although the complement system developed early in our evolutionary past as a protein-based method for targeting and destroying pathogens, it plays a critically important role following organ transplantation, a relatively new field that developed out of the first successful kidney transplant in 1954. According to research published by Llaudo et al in the American Journal of Transplantation the complement receptor C5a is important to heart transplant rejection in mice, a finding that has implications for human transplantation.

In mice, the long-term survival of heart transplants was previously demonstrated to depend upon the accumulation within the graft of an immunosuppressive blood cell population known as regulatory myeloid cells (Mregs), which prolong graft survival by promoting the expansion of anti-inflammatory regulatory T cells (Tregs) and inhibiting the activity of damaging effector T cells (Teffs).

Llaudo et al took this finding a step further, showing that Mregs lacking expression of the receptor for complement protein C5a (C5aR1) are not capable of migrating to the heart allograft, causing rejection to occur more quickly.

This finding contributes to our understanding of mechanisms regulating the development of an immunosuppressive intragraft microenvironment following the treatment of heart transplant recipients with costimulation-blockade therapy.

Studies that enhance our knowledge of immunological tolerance, such as this one, will perhaps one day permit the development of technology that allows for the complete acceptance of allografts by the human immune system, a holy grail of transplant research.

In addition to this article, some readers may find interest in another publication from the American Journal of Transplantation, which identified a role for the immunoproteosome in Carfilzomib resistance.

Llaudo I, Fribourg M, Medof ME, et al. (2019) C5aR1 regulates migration of suppressive myeloid cells required for costimulatory blockadeā€induced murine allograft survival. American Journal of Transplantation, 19(3):633-645.