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Prepublished online as a Blood First Edition Paper on June 21, 2002; DOI 10.1182/blood-2002-04-1036. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-04-1036v1 100/9/3269    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 Erickson, M. Articles by Farr, A. G. Search for Related Content PubMed PubMed Citation Articles by Erickson, M. Articles by Farr, A. G. Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 November 2002, Vol. 100, No. 9, pp. 3269-3278 IMMUNOBIOLOGY Regulation of thymic epithelium by keratinocyte growth factor Matthew Erickson, Stanislaw Morkowski, Sophie Lehar, Geoffrey Gillard, Courtney Beers, James Dooley, Jeffrey S. Rubin, Alexander Rudensky, and Andrew G. Farr From the Departments of Biological Structure and Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, WA; and the Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD. Here we demonstrate that keratinocyte growth factor (KGF) and FGFR2IIIb signaling can affect development and function of thymic epithelium (TE) and that -lineage thymocytes contribute to intrathymic levels of KGF. Thymocyte expression of KGF is developmentally regulated, being undetectable in CD348 thymocytes and expressed at highest levels by mature CD4 or CD8 thymocytes. Exposure of thymocyte-depleted fetal thymic lobes to KGF resulted in reduced thymic epithelial expression of class II major histocompatibility complex (MHC), invariant chain (Ii), and cathepsin L (CatL) molecules involved in thymocyte-positive selection and also stimulated expression of the cytokines interleukin 6 (IL-6) and thymic stromal-derived lymphopoietin (TSLP), while having little effect on IL-7 or stem cell factor expression. Within intact fetal thymic organ culture (FTOC), exogenous KGF impairs the generation of CD4 thymocytes. Two lines of evidence point to responsiveness of the medullary TE compartment to KGF and FGFR2IIIb signaling. First, the medullary compartment is expanded in intact FTOC exposed to KGF in vitro. Second, in the RAG-deficient thymus, where the thymocytes do not express detectable levels of KGF message, the hypoplastic medullary TE compartment can be expanded by administration of recombinant KGF in vivo. This expansion is accompanied by restoration of the normal profile of medullary TE-associated chemokine expression in the RAG2/ thymus. Collectively, these findings point to a role for KGF and FGFR signaling in the development and function of thymic epithelium. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. 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