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Blood, 1 December 2003, Vol. 102, No. 12, pp. 4115-4122. Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-01-0175. This Article Full Text 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 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 Ilangumaran, S. Articles by Rottapel, R. Search for Related Content PubMed PubMed Citation Articles by Ilangumaran, S. Articles by Rottapel, R. Related Collections Immunobiology Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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 From the Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto; Sunnybrook and Women's College Health Science Centre, Toronto; Departments of Immunology, Medicine, and Medical Biophysics, University of Toronto; and St Michael's Hospital, Toronto, Ontario, Canada. SOCS1-/- mice die prematurely of increased interferon- (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 toward 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 interleukin-7 (IL-7) signaling at the CD4-CD8- stage but is essential for regulating IL-15 and IL-2 signaling in CD8+ thymocytes. IL-15 selectively stimulates SOCS1-/- CD8+ thymocytes, inducing sustained signal transducer and activator of transcription 5 (STAT5) phosphorylation and massive proliferation. IL-15 also strongly up-regulates Bcl-xL and CD44 in CD8+ thymocytes lacking SOCS1. The SOCS1 gene is induced in CD4+ thymocytes by c cytokines, whereas CD8+ thymocytes constitutively express SOCS1 mRNA even in the absence of cytokine stimulation. Because many different cell types express IL-15, our results strongly suggest that SOCS1 functions as an indispensable attenuator of IL-15 receptor signaling in developing CD8+ thymocytes. (Blood. 2003;102:4115-4122) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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]

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