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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 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 Citation Map 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. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease Tangsheng Yi13, Dongchang Zhao2,3, Chia-Lei Lin2,3, Chunyan Zhang2,3, Ying Chen2,3, Ivan Todorov2, Thomas LeBon1, Fouad Kandeel2, Stephen Forman3, and Defu Zeng13 1 Graduate School of Biological Science, 2 Department of Diabetes, Endocrinology & Metabolism, and 3 Division of Hematology & Hematopoietic Cell Transplantation, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 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- 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- 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. 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. Drobyski Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease Blood, July 23, 2009; 114(4): 891 - 900. [Abstract] [Full Text] [PDF] S. von Vietinghoff and K. 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[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. Straus Differential Regulation of Chemokines by IL-17 in Colonic Epithelial Cells J. Immunol., November 1, 2008; 181(9): 6536 - 6545. [Abstract] [Full Text] [PDF]

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