The Impact of Regulated Cell Death Pathways on Alloimmune Responses and Graft Injury

Abstract Transplantation is invariably associated with organ injury following donor organ procurement. Death of cells can negatively impact organ function if sufficient numbers of parenchymal cells are eliminated and not replaced as part of remodelling. Additionally by the release of contents, the death of cells can alter immune responses that are related to ischemia-reperfusion injury and alloimmune rejection. There is increasing awareness of the link between innate and adaptive immunity, and the profound influence inflammation has on organ function, tolerance induction, rejection responses and perhaps survival. Unfortunately, long-term survival of transplants has not been greatly impacted by advances in transplant strategies that solely target recipient immune responses. Therefore, a focus on better understanding tissue injury, and characterizing how newly described forms of cell death influence inflammation in transplanted organs, is timely and likely to yield more effective strategies. Until recently, programmed cell death was relegated entirely to apoptosis, a form of death that is largely, but not exclusively, silent immunologically. In contrast, necrosis is highly pro-inflammatory, but has not been considered to be regulatable, and is thus beyond therapeutic targeting. This partitioning of cell death has become blurred as regulated forms of necrosis such as necroptosis have been identified and immune consequences of apoptosis are characterized. While ...
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research