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Blood, 1 September 2008, Vol. 112, No. 5, pp. 2101-2110. Prepublished online as a Blood First Edition Paper on July 2, 2008; DOI 10.1182/blood-2007-12-126987. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-12-126987v1 112/5/2101    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yi, T. Articles by Zeng, D. Search for Related Content PubMed PubMed Citation Articles by Yi, T. Articles by Zeng, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 3, 2007 Accepted June 3, 2008 Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft versus host disease Tangsheng Yi, Dongchang Zhao, Chia-Lei Lin, Chunyan Zhang, Ying Chen, Ivan Todorov, Thomas LeBon, Fouad Kandeel, Stephen Forman, and Defu Zeng* Graduate School of Biological Science, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States Department of Diabetes, Endocrinology & Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States Division of Hematology & Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States * Corresponding author; email: dzeng{at}coh.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 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- 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- 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Socie and B. R. Blazar Acute graft-versus-host disease: from the bench to the bedside Blood, November 12, 2009; 114(20): 4327 - 4336. [Abstract] [Full Text] [PDF] T. Yi, Y. Chen, L. Wang, G. Du, D. Huang, D. Zhao, H. Johnston, J. Young, I. Todorov, D. T. Umetsu, et al. Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease Blood, October 1, 2009; 114(14): 3101 - 3112. [Abstract] [Full Text] [PDF] X. Chen, R. Das, R. Komorowski, A. Beres, M. J. Hessner, M. Mihara, and W. R. 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Panoskaltsis-Mortari, B. R. Blazar, and J. S. Serody In vitro-differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations Blood, February 5, 2009; 113(6): 1365 - 1374. [Abstract] [Full Text] [PDF] N. Li, Y. Chen, W. He, T. Yi, D. Zhao, C. Zhang, C.-L. Lin, I. Todorov, F. Kandeel, S. Forman, et al. Anti-CD3 preconditioning separates GVL from GVHD via modulating host dendritic cell and donor T-cell migration in recipients conditioned with TBI Blood, January 22, 2009; 113(4): 953 - 962. [Abstract] [Full Text] [PDF] L. W. Kappel, G. L. Goldberg, C. G. King, D. Y. Suh, O. M. Smith, C. Ligh, A. M. Holland, J. Grubin, N. M. Mark, C. Liu, et al. IL-17 contributes to CD4-mediated graft-versus-host disease Blood, January 22, 2009; 113(4): 945 - 952. [Abstract] [Full Text] [PDF] J. W. Lee, P. Wang, M. G. Kattah, S. Youssef, L. Steinman, K. DeFea, and D. S. 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