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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3227-3233. Prepublished online as a Blood First Edition Paper on July 14, 2005; DOI 10.1182/blood-2005-02-0769. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-02-0769v1 106/9/3227    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 Yamaoka, K. Articles by O'Shea, J. J Search for Related Content PubMed PubMed Citation Articles by Yamaoka, K. Articles by O'Shea, J. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 24, 2005 Accepted June 16, 2005 Jak3 negatively regulates dendritic cell cytokine production and survival Kunihiro Yamaoka*, Booki Min, Yong-Jie Zhou, William E Paul, and John J O'Shea Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institute of Health, Bethesda, MD, USA Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, USA * Corresponding author; email: yamaokak{at}mail.nih.gov. Cytokines are critical in regulating the development and function of diverse cells. Jak3 is a tyrosine kinase expressed in hematopoietic cells, which associates with the common gamma receptor (c) and is required for signaling for a family of cytokines including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15 and IL-21; deficiency of either Jak3 or c results in severe combined immunodeficiency (SCID). While Jak3 is essential for lymphoid cell development, the potential roles for Jak3 in regulating dendritic cells (DCs) were unclear. Herein we show that although CD8+ CD11c+ splenic DCs are absent in Jak3-/- mice; bone marrow-derived DCs developed normally in vitro from Jak3-/- precursor cells. In fact, the survival of Jak3-/- DCs was enhanced and they expressed lower levels of pro-apoptotic proteins. Jak3-/- DCs exhibited normal antigen uptake and up-regulation of co-stimulatory molecules. However, Jak3-/-DCs produced more IL-12 and IL-10 in response to Toll-like receptor ligands, which correlated with enhanced Th1 differentiation in vivo. In summary, Jak3 is not essential for DC development, but unexpectedly appears to be an important negative regulator. These results may be relevant clinically for SCID patients who have undergone hematopoietic stem cell transplantation and for patients treated with Jak3 inhibitor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. De Trez, K. Schneider, K. Potter, N. Droin, J. Fulton, P. S. Norris, S.-w. Ha, Y.-X. Fu, T. Murphy, K. M. Murphy, et al. The Inhibitory HVEM-BTLA Pathway Counter Regulates Lymphotoxin Receptor Signaling to Achieve Homeostasis of Dendritic Cells J. Immunol., January 1, 2008; 180(1): 238 - 248. [Abstract] [Full Text] [PDF] J. R. Cortes, M. Perez-G, M. D. Rivas, and J. Zamorano Kaempferol Inhibits IL-4-Induced STAT6 Activation by Specifically Targeting JAK3 J. Immunol., September 15, 2007; 179(6): 3881 - 3887. [Abstract] [Full Text] [PDF] W. T. Watford, D. Li, D. Agnello, L. Durant, K. Yamaoka, Z. J. Yao, H.-J. Ahn, T. P. Cheng, S. R. Hofmann, T. Cogliati, et al. Cytohesin Binder and Regulator (Cybr) Is Not Essential for T- and Dendritic-Cell Activation and Differentiation. Mol. Cell. Biol., September 1, 2006; 26(17): 6623 - 6632. [Abstract] [Full Text] [PDF]

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