IL-17-producing γδT cells ameliorate intestinal acute graft-versus-host disease by recruitment of Gr-1+CD11b+ myeloid-derived suppressor cells

Abstract

Acute graft-versus-host disease (aGVHD) is the most severe complication and the major cause of morbidity and mortality in patients who have received hematopoietic stem cell transplantation. Inflammation mediated by donor T cells and neighboring recipient cells is considered to be responsible for intestinal aGVHD. Interleukin (IL)-17A-producing γδT (γδT17) cells have been investigated as key players in cancer, immunity, and inflammatory responses because of their phenotypic plasticity, memory-like activity, and unique migratory features. However, the precise roles and underlying mechanisms of γδT17 cells in aGVHD immunopathogenesis remain elusive. Here, we found that γδT17 cells constituted the major resident γδT population in the intestinal lamina propria of aGVHD mice. Adoptive infusion of induced γδT17 cells markedly attenuated murine aGVHD and increased infiltration of Gr-1⁺CD11b⁺ myeloid-derived suppressor cells (MDSCs) into the inflammatory intestine, and did not affect graft-versus-leukemia(GVL) effect. Further experiments indicated that γδT17 cells enhanced both migration ability and immunosuppressive activity of MDSCs. γδT17 cell-mediated protection in aGVHD was blunted by depletion of IL-17A or MDSCs. Our study clarifies an immune pathway where γδT17 cells play a protective role in murine aGVHD by recruiting MDSCs to the inflammatory intestine.