Interleukin 17 Is Not Required for Autoimmune-Mediated Pathologic Damage during Chronic Graft-versus-Host Disease

The transition from acute to chronic graft-versus-host disease (aGVHD, cGVHD) is characterized by the progressive loss of self-tolerance and the development of autoimmune manifestations. Interleukin 17 (IL-17) is a proinflammatory cytokine that has been shown to play a prominent role in autoimmune disorders in the nontransplant setting, but the extent to which IL-17 is necessary for the autoimmunity that occurs as a consequence of GVHD is not known. In this study, we demonstrate using a combination of antibody-based and genetic approaches that IL-17 is not required for the loss of self-tolerance and resulting CD4+ T cell-dependent pathologic damage that occurs during the evolution from aGVHD to cGVHD. Rather, TH1 cells and other proinflammatory cytokines are fully competent to promote autoimmune-mediated tissue damage. Thus, the selective targeting of IL-17 may not be a viable clinical strategy for preventing the autoimmune manifestations that develop during cGVHD.