The IL-17 Differentiation Pathway and Its Role in Transplant Outcome

The limitations of allogeneic transplantation are graft-versus-host disease (both acute and chronic), infection, and relapse. Acute GVHD has traditionally been thought of as a Th1-mediated disease with inflammatory cytokines (eg, inteferon [IFN]-γ and tumor necrosis factor [TNF]) and cellular cytolysis mediating apoptotic target tissue damage in skin, gut, and liver. Chronic GVHD has not fit neatly into either Th1 or Th2 (eg, IL-4, IL-13) paradigms. Increasingly, the Th17 pathway of differentiation has been shown to play important roles in acute and chronic GVHD (aGVHD, cGVHD), particularly in relation to skin and lung disease. Here we discuss the IL-17 pathway of T cell differentiation and the accumulating evidence suggesting it represents an important new target for the control of deleterious alloimmune responses.