| Title | Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft versus host disease. | | Author(s) | Yi T, Zhao D, Lin CL, Zhang C, Chen Y, Todorov I, Lebon T, Kandeel F, Forman S, Zeng D | | Institution | Graduate School of Biological Science, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States. | | Source | Blood 2008 Jul 2. | | 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 GVHD is still unknown. Here we showed that, in an acute GVHD model of C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient, IL-17(-/-) donor T cells manifested an augmented Th1 differentiation and IFN-gamma production and induced exacerbated acute GVHD. Severe tissue damage mediated by IL-17(-/-) donor T cells was associated with increased Th1 infiltration, upregulation of chemokine receptors by donor T cells, and enhanced tissue expression of inflammatory chemokines. Administration of recombinant IL-17 and neutralizing IFN-gamma 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 downregulate 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18596226 |
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