Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease

T Yi, D Zhao, CL Lin, C Zhang, Y Chen… - Blood, The Journal …, 2008 - ashpublications.org
T Yi, D Zhao, CL Lin, C Zhang, Y Chen, I Todorov, T LeBon, F Kandeel, S Forman, D Zeng
Blood, The Journal of the American Society of Hematology, 2008ashpublications.org
Th17 is a newly identified T-cell lineage that secretes proinflammatory cytokine IL-17. Th17
cells have been shown to play a critical role in mediating autoimmune diseases such as
EAE, colitis, and arthritis, but their role in the pathogenesis of graft-versus-host disease
(GVHD) is still unknown. Here we showed that, in an acute GVHD model of C57BL/6 (H-2b)
donor to BALB/c (H-2d) recipient, IL-17−/− donor T cells manifested an augmented Th1
differentiation and IFN-γ production and induced exacerbated acute GVHD. Severe tissue …
Abstract
Th17 is a newly identified T-cell lineage that secretes proinflammatory cytokine IL-17. Th17 cells have been shown to play a critical role in mediating autoimmune diseases such as EAE, colitis, and arthritis, but their role in the pathogenesis of graft-versus-host disease (GVHD) is still unknown. Here we showed that, in an acute GVHD model of C57BL/6 (H-2b) donor to BALB/c (H-2d) recipient, IL-17−/− donor T cells manifested an augmented Th1 differentiation and IFN-γ production and induced exacerbated acute GVHD. Severe tissue damage mediated by IL-17−/− donor T cells was associated with increased Th1 infiltration, up-regulation of chemokine receptors by donor T cells, and enhanced tissue expression of inflammatory chemokines. Administration of recombinant IL-17 and neutralizing IFN-γ in the recipients given IL-17−/− donor cells ameliorated the acute GVHD. Furthermore, the regulation of Th1 differentiation by IL-17 or Th17 may be through its influence on host DCs. Our results indicate that donor Th17 cells can down-regulate Th1 differentiation and ameliorate acute GVHD in allogeneic recipients, and that treatments neutralizing proinflammatory cytokine IL-17 may augment acute GVHD as well as other inflammatory autoimmune diseases.
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