The role of danger signals and ectonucleotidases in acute graft-versus-host disease

Allogeneic hematopoietic cell transplantation (allo-HCT) represents the only curative treatment approach for many patients with benign or malignant diseases of the hematopoietic system. However, post-transplant morbidity and mortality are significantly increased by the development of acute graft-versus-host disease (GvHD). While alloreactive T cells act as the main cellular mediator of the GvH reaction, recent evidence suggests a critical role of the innate immune system in the early stages of GvHD initiation. Danger-associated molecular patterns released from the intracellular space as well as from the extracellular matrix activate antigen-presenting cells and set pro-inflammatory pathways in motion. This review gives an overview about danger signals representing therapeutic targets with a clinical perspective with a particular focus on extracellular nucleotides and ectonucleotidases.