Necroptosis in Solid Organ Transplantation: A Literature Overview

Ischemia-reperfusion injury (IRI) is encountered in various stages during solid organ transplantation (SOT). IRI is known to be a multifactorial inflammatory condition involving hypoxia, metabolic stress, leukocyte extravasation, cellular death (including apoptosis, necrosis and necroptosis) and an activation of immune response. Although the cycle of sterile inflammation during IRI is consistent among different organs, the underlying mechanisms are poorly understood. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be crucial in the implementation of necroptosis. Moreover, apart from silent apoptotic death, necrosis also causes sterile inflammation-necroinflammation, which is triggered by various damage-associated molecular patterns (DAMPs). Those DAMPs activate the innate immune system, causing local and systemic inflammatory responses, which can result in graft failure. In this overview we summarize knowledge on mechanisms of sterile inflammation processes during SOT with special focus on necroptosis and IRI and discuss protective strategies.

Automated summary

Ischemia-reperfusion injury (IRI) is a common problem during solid organ transplantation (SOT), characterized by multifactorial inflammatory responses. Mixed-lineage kinase domain-like pseudokinase (MLKL) and receptor-interacting protein kinase 3 (RIPK3) play crucial roles in necroptosis. Necrosis also triggers sterile inflammation, leading to graft failure.