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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3757-3766. Prepublished online as a Blood First Edition Paper on January 16, 2007; DOI 10.1182/blood-2006-07-037655. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-037655v1 109/9/3757    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 Rowbotham, N. J. Articles by Crompton, T. Search for Related Content PubMed PubMed Citation Articles by Rowbotham, N. J. Articles by Crompton, T. Related Collections Immunobiology Signal Transduction Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation Nicola J. Rowbotham1, Ariadne L. Hager-Theodorides1, Marek Cebecauer2, Divya K. Shah1, Ekati Drakopoulou1, Julian Dyson3, Susan V. Outram1, and Tessa Crompton1 1 Division of Cell and Molecular Biology, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, United Kingdom; 2 Section of Molecular and Cellular Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, United Kingdom; 3 Department of Immunology, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom TCR signal strength is involved in many cell fate decisions in the T-cell lineage. Here, we show that transcriptional events induced by Hedgehog (Hh) signaling reduced TCR signal strength in mice. Activation of Hh signaling in thymocytes in vivo by expression of a transgenic transcriptional-activator form of Gli2 (Gli2N2) changed the outcome of TCR ligation at many stages of thymocyte development, allowing self-reactive cells to escape clonal deletion; reducing transgenic TCR-mediated positive selection; reducing the ratio of CD4/CD8 single-positive (SP) cells; and reducing cell surface CD5 expression. In contrast, in the Shh–/– thymus the ratio of CD4/CD8 cells and both positive and negative selection of a transgenic TCR were increased, demonstrating that Shh does indeed influence TCR repertoire selection and the transition from double-positive (DP) to SP cell in a physiological situation. In peripheral T cells, Gli2N2 expression attenuated T-cell activation and proliferation, by a mechanism upstream of ERK phosphorylation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Glis: novel modulators of TCR signaling? Ursula Bommhardt Blood 2007 109: 3618-3619. [Full Text] [PDF] This article has been cited by other articles: A. Varas, C. Hernandez-Lopez, J. Valencia, S. Mattavelli, V. G. Martinez, L. Hidalgo, C. Gutierrez-Frias, A. G. Zapata, R. Sacedon, and A. Vicente Survival and function of human thymic dendritic cells are dependent on autocrine Hedgehog signaling J. Leukoc. Biol., June 1, 2008; 83(6): 1476 - 1483. [Abstract] [Full Text] [PDF] M. Kobune, J. Kato, Y. Kawano, K. Sasaki, H. Uchida, K. Takada, S. Takahashi, R. Takimoto, and Y. Niitsu Adenoviral Vector-Mediated Transfer of the Indian Hedgehog Gene Modulates Lymphomyelopoiesis In Vivo Stem Cells, February 1, 2008; 26(2): 534 - 542. [Abstract] [Full Text] [PDF] A. Uhmann, K. Dittmann, F. Nitzki, R. Dressel, M. Koleva, A. Frommhold, A. Zibat, C. Binder, I. Adham, M. Nitsche, et al. The Hedgehog receptor Patched controls lymphoid lineage commitment Blood, September 15, 2007; 110(6): 1814 - 1823. [Abstract] [Full Text] [PDF]

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