SEARCH:   Advanced

Blood, 1 October 2008, Vol. 112, No. 7, pp. 2836-2846. Prepublished online as a Blood First Edition Paper on July 24, 2008; DOI 10.1182/blood-2008-04-149435. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-149435v1 112/7/2836    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 Chu, Y.-W. Articles by Gress, R. E. Search for Related Content PubMed PubMed Citation Articles by Chu, Y.-W. Articles by Gress, R. E. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion Yu-Waye Chu1, Sabrina Schmitz1, Baishakhi Choudhury1, William Telford1, Veena Kapoor1, Susan Garfield2, David Howe1, and Ronald E. Gress1 1 Experimental Transplantation and Immunology Branch, Center for Cancer Research, and 2 Laboratory of Experimental Carcinogenesis, National Institutes of Health (NIH), Bethesda, MD Insulin-like growth factor 1 (IGF-1) enhances thymopoiesis but given the broad distribution of IGF-1 receptors (IGF-1Rs), its mechanism of action has remained unclear. To identify points of thymic regulation by IGF-1, we examined its effects on T-cell precursors, thymocytes, and thymic epithelial cells (TECs) in normal and genetically altered mice. In thymus-intact but not thymectomized mice, IGF-1 administration increased peripheral naive and recent thymic emigrant (RTE) populations, demonstrating its effect on T-cell production, not peripheral expansion. IGF-1 administration increased bone marrow LSK (lineage–, Sca-1+, c-kit+) precursor proliferation and peripheral LSK populations, increased thymocyte populations in a sequential wave of expansion, and proportionately expanded TEC subpopulations and enhanced their chemokine expression. To separate IGF-1's effects on thymocytes and TECs, we generated mice lacking IGF-1R on thymocytes and T cells. Thymocyte and RTE numbers were decreased in these mice, but IGF-1 treatment produced comparable thymocyte numbers to similarly treated wild-type mice. We additionally separated thymic- from LSK-specific effects by demonstrating that IGF-1 increased thymocyte numbers despite impaired early thymic progenitor (ETP) importation in PSGL-1KO mice. These results indicate the critical point thymic function regulation by IGF-1 involves TEC expansion regulating thymocyte precursor entry and facilitating thymocyte development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Yang, Y.-H. Youm, Y. Sun, J.-S. Rim, C. J. Galban, B. Vandanmagsar, and V. D. Dixit Axin expression in thymic stromal cells contributes to an age-related increase in thymic adiposity and is associated with reduced thymopoiesis independently of ghrelin signaling J. Leukoc. Biol., June 1, 2009; 85(6): 928 - 938. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020