Adoptively transferred donor IL-17-producing CD4+ T cells augment, but IL-17 alleviates, acute graft-versus-host disease

Y Cai, S Ma, Y Liu, H Gong, Q Cheng, B Hu… - Cellular & molecular …, 2018 - nature.com
Y Cai, S Ma, Y Liu, H Gong, Q Cheng, B Hu, Y Wu, X Yu, C Dong, K Sun, D Wu, H Liu
Cellular & molecular immunology, 2018nature.com
The role of IL-17 and IL-17-producing CD4+ T cells in acute graft-versus-host disease
(GVHD) has been controversial in recent mouse and human studies. We carried out studies
in a murine acute GVHD model of fully major histocompatibility complex-mismatched
myeloablative bone marrow transplantation. We showed that donor wild-type CD4+ T cells
exacerbated acute GVHD compared with IL-17−/− CD4+ T cells, while IL-17 reduced the
severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17 …
Abstract
The role of IL-17 and IL-17-producing CD4+ T cells in acute graft-versus-host disease (GVHD) has been controversial in recent mouse and human studies. We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation. We showed that donor wild-type CD4+ T cells exacerbated acute GVHD compared with IL-17−/− CD4+ T cells, while IL-17 reduced the severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17-producing CD4+ T cells was associated with increased Th1 responses, while IL-17 decreased the percentages of Th1 cells in the GVHD target organs. Furthermore, IL-17 reduced the infiltration of macrophages into the GVHD tissues. In vitro study showed that IL-17 could downregulate Th1 responses, possibly through inhibiting IL-12 production by donor macrophages. Depletion of macrophages in vivo diminished the protective effect of IL-17. Our results demonstrated the differential roles of adoptively transferred donor IL-17-producing CD4+ T cells and IL-17 in the same acute GVHD model.
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