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Blood, 15 July 2007, Vol. 110, No. 2, pp. 553-560. Prepublished online as a Blood First Edition Paper on March 29, 2007; DOI 10.1182/blood-2006-11-059246. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-11-059246v1 110/2/553    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 Tokumasa, N. Articles by Nakajima, H. Search for Related Content PubMed PubMed Citation Articles by Tokumasa, N. Articles by Nakajima, H. Related Collections Immunobiology Gene Expression Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN- production and the induction of Th1 cell differentiation Naoki Tokumasa1, Akira Suto2, Shin-ichiro Kagami2, Shunsuke Furuta1, Koichi Hirose1, Norihiko Watanabe1, Yasushi Saito1, Kazuya Shimoda3, Itsuo Iwamoto4, and Hiroshi Nakajima2 1 Department of Allergy and Clinical Immunology, Clinical Cell Biology, 2 Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Japan; 3 Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Japan; 4 Research Center for Allergy and Clinical Immunology, Asahi General Hospital, Chiba, Japan It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2–/–) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2–/– DCs. IL-12–induced IFN- production was also significantly diminished in Tyk2–/– DCs to levels similar to those in Stat4–/– DCs. Interestingly, Tyk2–/– DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2–/– DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN- from DCs and thereby for the induction of antigen-specific Th1-cell differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Arima, N. Watanabe, S. Hanabuchi, M. Chang, S.-C. Sun, and Y.-J. Liu Distinct Signal Codes Generate Dendritic Cell Functional Plasticity Sci. Signal., January 19, 2010; 3(105): ra4 - ra4. [Abstract] [Full Text] [PDF] A. J. Bieber, K. Suwansrinon, J. Kerkvliet, W. Zhang, L. R. Pease, and M. Rodriguez Allelic variation in the Tyk2 and EGF genes as potential genetic determinants of CNS repair PNAS, January 12, 2010; 107(2): 792 - 797. [Abstract] [Full Text] [PDF] A. Oyamada, H. Ikebe, M. Itsumi, H. Saiwai, S. Okada, K. Shimoda, Y. Iwakura, K. I. Nakayama, Y. Iwamoto, Y. Yoshikai, et al. Tyrosine Kinase 2 Plays Critical Roles in the Pathogenic CD4 T Cell Responses for the Development of Experimental Autoimmune Encephalomyelitis J. Immunol., December 1, 2009; 183(11): 7539 - 7546. [Abstract] [Full Text] [PDF] K. M. Spach, R. Noubade, B. McElvany, W. F. Hickey, E. P. Blankenhorn, and C. Teuscher A Single Nucleotide Polymorphism in Tyk2 Controls Susceptibility to Experimental Allergic Encephalomyelitis J. Immunol., June 15, 2009; 182(12): 7776 - 7783. [Abstract] [Full Text] [PDF] S. Verstovsek Therapeutic potential of JAK2 inhibitors Hematology, January 1, 2009; 2009(1): 636 - 642. [Abstract] [Full Text] [PDF] H. Wakashin, K. Hirose, Y. Maezawa, S.-i. Kagami, A. Suto, N. Watanabe, Y. Saito, M. Hatano, T. Tokuhisa, Y. Iwakura, et al. IL-23 and Th17 Cells Enhance Th2-Cell-mediated Eosinophilic Airway Inflammation in Mice Am. J. Respir. Crit. Care Med., November 15, 2008; 178(10): 1023 - 1032. [Abstract] [Full Text] [PDF] R. Nakamura, K. Shibata, H. Yamada, K. Shimoda, K. Nakayama, and Y. Yoshikai Tyk2-Signaling Plays an Important Role in Host Defense against Escherichia coli through IL-23-Induced IL-17 Production by {gamma}{delta} T Cells J. Immunol., August 1, 2008; 181(3): 2071 - 2075. [Abstract] [Full Text] [PDF]

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