Figure 2.

DAMP may contribute to CR after Tx in several scenarios. (A) The alloreactive response of innate and adaptive cells may sustain the pro-inflammatory phase and lead to a failure to fully transition through the resolution phase and complete the repair phase. In this scenario, CR represents a failure to resolve and repair, leading to residual graft damage and failure to restore tissue homeostasis. Alternatively, these changes may cause an overzealous counter-responses initiated by reparative Treg and reparative macrophages in responses to regulatory and reparative DAMPs released by an unresolved allogeneic wound. (B) Alternatively, lost or depleted reparative and regulatory cells due to ischemia or alloimmune responses may lead to a failed resolution phase leading to residual graft damage. This scenario may also arise from a depletion of local reparative and regulatory DAMPs over time. In this case, CR would represent a failure to restore tissue homeostasis due to persisting graft damage.