Role of TLRs and DAMPs in allograft inflammation and transplant outcomes

Graft necrosis resulting from ischaemia–reperfusion injury leads to the release of endogenous molecules — damage-associated molecular patterns (DAMPs) — which trigger a sterile inflammatory reaction. The resulting immune response can impair transplant tolerance or result in acute or chronic graft rejection. In this Review, Braza et al. discuss the nature of DAMPs and their downstream signalling pathways, with a focus on Toll-like receptors. They outline various strategies to inhibit DAMP-induced inflammation with the aim of improving the outcomes of solid organ transplantation, and discuss the challenge of inhibiting the innate immune response within the graft without compromising the patient's response to pathogens.