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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3803-3811. Prepublished online as a Blood First Edition Paper on January 9, 2007; DOI 10.1182/blood-2006-10-049767. This Article Full Text (PDF) All Versions of this Article: blood-2006-10-049767v1 109/9/3803    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 Rossi, S. W. Articles by Hollander, G. A. Search for Related Content PubMed PubMed Citation Articles by Rossi, S. W. Articles by Hollander, G. A. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 2, 2006 Accepted December 22, 2006 Keratinocyte growth factor (KGF) enhances postnatal T- cell development via enhancements in proliferation and function of thymic epithelial cells Simona W. Rossi, Lukas T. Jeker, Tomoo Ueno, Sachiyo Kuse, Marcel P. Keller, Saulius Zuklys, Andrei V. Gudkov, Yousuke Takahama, Werner Krenger, Bruce R. Blazar, and Georg A. Hollander* Laboratory of Pediatric Immunology, Center for Biomedicine, Dept of Clinical-Biological Sciences, University of Basel & University Children's Hospital (UKBB), Basel, Switzerland Division of Experiemental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan Dept of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United States Dept of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis, MN, United States * Corresponding author; email: georg-a.hollaender{at}unibas.ch. The systemic administration of keratinocyte growth factor (KGF) enhances T-cell lymphopoiesis in normal and bone marrow transplanted mice and exerts protection to thymic stromal cells from cytoablative conditioning and graft-versus-host disease-induced injury. However, little is known regarding KGF's molecular and cellular mechanisms of action on thymic stromal cells. Here we report that KGF induces in vivo a transient expansion of both mature and immature thymic epithelial cells (TECs) and promotes the differentiation of the latter type of cells. The increased TEC numbers return within two weeks to normal values and the microenvironment displays a normal architectural organization. Stromal changes initiate an expansion of immature thymocytes and permit regular T-cell development at an increased rate and for an extended period of time. KGF signaling in TECs activates both the p53 and NF-B pathways and results in the transcription of several target genes necessary for TEC function and T-cell development, including bone morphogenetic protein (BMP)-2, BMP-4, Wnt5b and Wnt10b. Signaling via the canonical BMP pathway is critical for the KGF effects. Taken together, these data provide new insights into the mechanism(s) of action of exogenous KGF on TEC function and thymopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: KGF boosts thymic archiTECture Yu-Waye Chu and Frances T. Hakim Blood 2007 109: 3613-3614. [Full Text] [PDF] This article has been cited by other articles: M. Bruinsma, P. L. van Soest, P. J. M. Leenen, B. Lowenberg, J. J. Cornelissen, and E. Braakman Keratinocyte Growth Factor Improves Allogeneic Bone Marrow Engraftment through a CD4+Foxp3+ Regulatory T Cell-Dependent Mechanism J. Immunol., June 15, 2009; 182(12): 7364 - 7369. [Abstract] [Full Text] [PDF] D. A. Sultana, S. Tomita, M. Hamada, Y. Iwanaga, Y. Kitahama, N. Van Khang, S. Hirai, I. Ohigashi, S. Nitta, T. Amagai, et al. Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development Blood, March 26, 2009; 113(13): 2976 - 2987. [Abstract] [Full Text] [PDF] S. Zuklys, J. Gill, M. P. Keller, M. Hauri-Hohl, S. Zhanybekova, G. Balciunaite, K.-J. Na, L. T. Jeker, K. Hafen, N. Tsukamoto, et al. Stabilized {beta}-Catenin in Thymic Epithelial Cells Blocks Thymus Development and Function J. Immunol., March 1, 2009; 182(5): 2997 - 3007. [Abstract] [Full Text] [PDF] R. R. Jenq, C. G. King, C. Volk, D. Suh, O. M. Smith, U. K. Rao, N. L. Yim, A. M. Holland, S. X. Lu, J. L. Zakrzewski, et al. Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation Blood, February 12, 2009; 113(7): 1574 - 1580. [Abstract] [Full Text] [PDF] J. Dooley, M. Erickson, and A. G. Farr Alterations of the Medullary Epithelial Compartment in the Aire-Deficient Thymus: Implications for Programs of Thymic Epithelial Differentiation J. Immunol., October 15, 2008; 181(8): 5225 - 5232. [Abstract] [Full Text] [PDF] K. M. Williams, P. J. Lucas, C. V. Bare, J. Wang, Y.-W. Chu, E. Tayler, V. Kapoor, and R. E. Gress CCL25 increases thymopoiesis after androgen withdrawal Blood, October 15, 2008; 112(8): 3255 - 3263. [Abstract] [Full Text] [PDF] Y.-W. Chu, S. Schmitz, B. Choudhury, W. Telford, V. Kapoor, S. Garfield, D. Howe, and R. E. Gress Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion Blood, October 1, 2008; 112(7): 2836 - 2846. [Abstract] [Full Text] [PDF] M. M. Hauri-Hohl, S. Zuklys, M. P. Keller, L. T. Jeker, T. Barthlott, A. M. Moon, J. Roes, and G. A. Hollander TGF-{beta} signaling in thymic epithelial cells regulates thymic involution and postirradiation reconstitution Blood, August 1, 2008; 112(3): 626 - 634. [Abstract] [Full Text] [PDF] M. G. L. Depreter, N. F. Blair, T. L. Gaskell, C. S. Nowell, K. Davern, A. Pagliocca, F. H. Stenhouse, A. M. Farley, A. Fraser, J. Vrana, et al. Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells PNAS, January 22, 2008; 105(3): 961 - 966. [Abstract] [Full Text] [PDF] M. Guimond, W. J. Leonard, R. Spolski, S. W. Rossi, R. G. Veenstra, G. A. Hollander, C. L. Mackall, and B. R. Blazar Thymic stromal lymphopoietin is not necessary or sufficient to mediate the thymopoietic effects of keratinocyte growth factor Blood, January 15, 2008; 111(2): 969 - 970. [Full Text] [PDF] M. Bruinsma, P. L. van Soest, P. J. M. Leenen, B. N. Lambrecht, T. Cupedo, B. Lowenberg, J. J. Cornelissen, and E. Braakman Keratinocyte Growth Factor Induces Expansion of Murine Peripheral CD4+Foxp3+ Regulatory T Cells and Increases Their Thymic Output J. Immunol., December 1, 2007; 179(11): 7424 - 7430. [Abstract] [Full Text] [PDF] M. M. Hauri-Hohl, M. P. Keller, J. Gill, K. Hafen, E. Pachlatko, T. Boulay, A. Peter, G. A. Hollander, and W. Krenger Donor T-cell alloreactivity against host thymic epithelium limits T-cell development after bone marrow transplantation Blood, May 1, 2007; 109(9): 4080 - 4088. [Abstract] [Full Text] [PDF]

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