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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1668-1675. Prepublished online as a Blood First Edition Paper on May 17, 2005; DOI 10.1182/blood-2004-08-3049. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2004-08-3049v1 106/5/1668    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 Chong, M. M Articles by Kay, T. W Search for Related Content PubMed PubMed Citation Articles by Chong, M. M Articles by Kay, T. W Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 6, 2004 Accepted April 28, 2005 Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammation Mark M Chong, Donald Metcalf, Emma Jamieson, Warren S Alexander, and Thomas W Kay* St. Vincent's Institute, Fitzroy, Victoria, Australia; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia St. Vincent's Institute, Fitzroy, Victoria, Australia * Corresponding author; email: tkay{at}svi.edu.au. The balance between pro- and anti-inflammatory cytokines modulates inflammation. Intracellular inhibitors of signaling in turn, contribute to the negative regulation of cytokines. One of these inhibitors is Suppressor of Cytokine Signaling-1 (SOCS-1). Socs1-/- mice die by three weeks of age with inflammation and fatty necrosis of the liver. Here, cre/loxP deletion of Socs1 was employed to investigate the contribution of specific cells/tissues to inflammatory disease. Mice with SOCS-1 deficiency in myeloid and lymphoid cells, but not lymphoid alone, became ill at 50-250 days of age. These mice developed splenomegaly and T cell/macrophage infiltration of many organs, including liver, lung, pancreas and muscle. There were also abnormally high levels of the pro-inflammatory cytokines IFN, TNF and IL-12, and activated T cells circulating in these mice. Socs1null T cells were found to be hypersensitive to multiple cytokines, including IL-1, IL-2 and IL-12, resulting in IFN production without requiring TCR ligation. Additionally, Socs1null macrophages produced excessive amounts of IL-12 and TNF in response to other cytokines, including IFN. A dysregulated cytokine network between T cells and macrophages is thus associated with this inflammatory disease. These findings indicate that SOCS-1 is critical in both T cells and macrophages for preventing uncontrolled inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. S. Almeida, P. M. Lago, N. Boechat, R. C. Huard, L. C. O. Lazzarini, A. R. Santos, M. Nociari, H. Zhu, B. M. Perez-Sweeney, H. Bang, et al. Tuberculosis Is Associated with a Down-Modulatory Lung Immune Response That Impairs Th1-Type Immunity J. Immunol., July 1, 2009; 183(1): 718 - 731. [Abstract] [Full Text] [PDF] W. Xiong, H. Wang, H. Wu, Y. Chen, and D. Han Apoptotic spermatogenic cells can be energy sources for Sertoli cells Reproduction, March 1, 2009; 137(3): 469 - 479. [Abstract] [Full Text] [PDF] H. Wu, H. Wang, W. Xiong, S. Chen, H. Tang, and D. Han Expression Patterns and Functions of Toll-Like Receptors in Mouse Sertoli Cells Endocrinology, September 1, 2008; 149(9): 4402 - 4412. [Abstract] [Full Text] [PDF] K.-S. Choi, E.-K. Song, and C.-Y. Yim Cytokines secreted by IL-2-activated lymphocytes induce endogenous nitric oxide synthesis and apoptosis in macrophages J. Leukoc. Biol., June 1, 2008; 83(6): 1440 - 1450. [Abstract] [Full Text] [PDF] R. Bianchini, G. Nocentini, L. T. Krausz, K. Fettucciari, S. Coaccioli, S. Ronchetti, and C. Riccardi Modulation of Pro- and Antiapoptotic Molecules in Double-Positive (CD4+CD8+) Thymocytes following Dexamethasone Treatment J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 887 - 897. [Abstract] [Full Text] [PDF] S. McGrath-Morrow, B. Laube, S.-C. Tzou, C. Cho, J. Cleary, H. Kimura, N. R. Rose, and P. Caturegli IL-12 overexpression in mice as a model for Sjogren lung disease Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L837 - L846. [Abstract] [Full Text] [PDF] H. Wang, H. Wang, W. Xiong, Y. Chen, Q. Ma, J. Ma, Y. Ge, and D. Han Evaluation on the phagocytosis of apoptotic spermatogenic cells by Sertoli cells in vitro through detecting lipid droplet formation by Oil Red O staining. Reproduction, September 1, 2006; 132(3): 485 - 492. [Abstract] [Full Text] [PDF]

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