Equipping the islet graft for self defence: targeting nuclear factor κb and implications for tolerance

Clinical islet transplantation does not enjoy the success seen for solid organ transplants, indicating a need for new therapeutic approaches to improve patient outcomes. This has prompted investigation into islet autonomous factors and pathways that may represent druggable targets. These have the potential to synergize with approaches aimed at generating graft-specific tolerance.There are emerging data that nuclear factor κB (NF-κB) activation can prevent and or overcome tolerance, whereas dampening NF-κB activation in immune cells is associated with prolonged allograft survival. In islet cells, NF-κB plays a central role in triggering the inflammatory transcriptional response that is often associated with reduced islet function and contributes to poor transplant outcomes.Targeting intraislet NF-κB represents a promising target in islet transplantation. Here we will discuss the current state of the knowledge on the role of NF-κB activation in the context of islet transplantation and the implications of targeting NF-κB for tolerance induction.Zammit, Nathan W., Grey, Shane T