IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease

Abstract

Significance This study reveals that the tryptophan-degrading reaction catalyzed by indoleamine 2,3-dioxygenase 1 (IDO1) is linked to reactive oxygen species (ROS) scavenging in Gr-1 + CD11b + myeloid cells. The IDO1-mediated ROS scavenging promotes myeloid-derived suppressor cell characteristics in Gr-1 + CD11b + cells, suppressing their differentiation into proinflammatory neutrophils. These results could explain the increased lethality in graft-versus-host disease as well as the enhanced proinflammatory and reduced regulatory T cell responses after transplantation of IDO1-deficient bone marrow cells. Our findings provide a mechanistic insight into the immune-modulatory roles of IDO1.