SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-01-0175. This Article Full Text (PDF) All Versions of this Article: 2003-01-0175v1 102/12/4115    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 Ilangumaran, S. Articles by Rottapel, R. Search for Related Content PubMed PubMed Citation Articles by Ilangumaran, S. Articles by Rottapel, R. Social Bookmarking                   What's this? Submitted February 4, 2003 Accepted July 25, 2003 Suppressor of cytokine signaling 1 attenuates IL-15 receptor signaling in CD8+ thymocytes Subburaj Ilangumaran, Sheela Ramanathan, Terry Ning, Jose La Rose, Brandon Reinhart, Philippe Poussier, and Robert Rottapel* Department of Experimental Therapeutics, Ontario Cancer Institute, Toronto, ON, Canada; Department of Rhematology, St. Michael's Hospital, Toronto, ON, Canada Department of Immunology, Sunnybrook and Women's College Health Science Centre, Toronto, ON, Canada * Corresponding author; email: rottapel{at}uhnres.utoronto.ca. SOCS1-/- mice die prematurely from increased IFN signaling with severe thymic atrophy and accelerated maturation of T cells. However, it was unclear whether the thymic defects were caused by SOCS1 deficiency or by increased IFN signaling. Using SOCS1-/-IFN-/- mice, we show in this study that SOCS1 deficiency skews thymocyte development towards CD8 lineage independently of IFN. Fetal thymic organ cultures and intrathymic transfer of CD4-CD8- precursors into Rag1-/- mice show that the lineage skewing in SOCS1-/- mice is a T cell autonomous defect. Interestingly, SOCS1 is not required for attenuating IL-7 signaling at the CD4-CD8- stage but is essential to regulate IL-15 and IL-2 signaling in CD8+ thymocytes. IL-15 selectively stimulates SOCS1-/- CD8+ thymocytes inducing sustained STAT5 phosphorylation and massive proliferation. IL-15 also strongly upregulates Bcl-xL and CD44 in CD8+ thymocytes lacking SOCS1. SOCS1 gene is induced in CD4+ thymocytes by c cytokines, whereas CD8+ thymocytes constitutively express SOCS1 mRNA even in the absence of cytokine stimulation. Since IL-15 is expressed by many different cell types, our results strongly suggest that SOCS1 functions as an indispensable attenuator of IL-15 receptor signaling in developing CD8+ thymocytes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Starr, M. Fuchsberger, L. S. Lau, A. P. Uldrich, A. Goradia, T. A. Willson, A. M. Verhagen, W. S. Alexander, and M. J. Smyth SOCS-1 Binding to Tyrosine 441 of IFN-{gamma} Receptor Subunit 1 Contributes to the Attenuation of IFN-{gamma} Signaling In Vivo J. Immunol., October 1, 2009; 183(7): 4537 - 4544. [Abstract] [Full Text] [PDF] A. Saudemont, A. Hamrouni, P. Marchetti, J. Liu, N. Jouy, D. Hetuin, F. Colucci, and B. Quesnel Dormant Tumor Cells Develop Cross-Resistance to Apoptosis Induced by CTLs or Imatinib Mesylate via Methylation of Suppressor of Cytokine Signaling 1 Cancer Res., May 1, 2007; 67(9): 4491 - 4498. [Abstract] [Full Text] [PDF] S. Ramanathan, J. Gagnon, C. Leblanc, R. Rottapel, and S. Ilangumaran Suppressor of Cytokine Signaling 1 Stringently Regulates Distinct Functions of IL-7 and IL-15 In Vivo during T Lymphocyte Development and Homeostasis J. Immunol., April 1, 2006; 176(7): 4029 - 4041. [Abstract] [Full Text] [PDF] G. M. Davey, R. Starr, A. L. Cornish, J. T. Burghardt, W. S. Alexander, F. R. Carbone, C. D. Surh, and W. R. Heath SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential J. Exp. Med., October 17, 2005; 202(8): 1099 - 1108. [Abstract] [Full Text] [PDF] T. Hanada, K. Tanaka, Y. Matsumura, M. Yamauchi, H. Nishinakamura, H. Aburatani, R. Mashima, M. Kubo, T. Kobayashi, and A. Yoshimura Induction of Hyper Th1 Cell-Type Immune Responses by Dendritic Cells Lacking the Suppressor of Cytokine Signaling-1 Gene J. Immunol., April 1, 2005; 174(7): 4325 - 4332. [Abstract] [Full Text] [PDF] O. Alpdogan, J. M. Eng, S. J. Muriglan, L. M. Willis, V. M. Hubbard, K. H. Tjoe, T. H. Terwey, A. Kochman, and M. R. M. van den Brink Interleukin-15 enhances immune reconstitution after allogeneic bone marrow transplantation Blood, January 15, 2005; 105(2): 865 - 873. [Abstract] [Full Text] [PDF] A. Yoshimura, H. M. M. Ohishi, D. Aki, and T. Hanada Regulation of TLR signaling and inflammation by SOCS family proteins J. Leukoc. Biol., March 1, 2004; 75(3): 422 - 427. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020