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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2678-2686. Prepublished online as a Blood First Edition Paper on June 22, 2006; DOI 10.1182/blood-2006-04-015404. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-015404v1 108/8/2678    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 Shi, L. Articles by Cao, X. Search for Related Content PubMed PubMed Citation Articles by Shi, L. Articles by Cao, X. Related Collections Signal Transduction Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY DIgR2, dendritic cell-derived immunoglobulin receptor 2, is one representative of a family of IgSF inhibitory receptors and mediates negative regulation of dendritic cell-initiated antigen-specific T-cell responses Liyun Shi, Kun Luo, Dajing Xia, Taoyong Chen, Guoyou Chen, Yingming Jiang, Nan Li, and Xuetao Cao From the Institute of Immunology, Zhejiang University, Hangzhou; and the Institute of Immunology and State Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, People's Republic of China. Dendritic cells (DCs) are specialized antigen-presenting cells that play crucial roles in the initiation and regulation of immune responses. Maturation and activation of DCs are controlled by a balance of the inhibitory and activating signals transduced through distinct surface receptors. Many inhibitory receptors expressed by DCs have been identified, whereas the new members and their functions need further investigation. In this study, we functionally characterized DC-derived immunoglobulin receptor 2 (DIgR2) as a novel representative of a family of inhibitory receptors belonging to the immunoglobulin superfamily. We show that DIgR2 contains 2 immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within its cytoplasmic region and that DIgR2 associates with Src homology-2 domain-containing protein tyrosine phosphatases-1 (SHP-1). Blockade of DIgR2 on DCs by pretreatment with DIgR2-Ig fusion protein or by silencing with specific small interfering RNA enhances DC-initiated T-cell proliferation and antigen-specific T-cell responses both in vitro and in vivo. Furthermore, immunization of mice with antigen-pulsed, DIgR2-silenced DCs elicits more potent antigen-specific CD4+ and CD8+ T-cell responses, thus protecting the vaccinated mice from tumor challenge more effectively. Our data suggest that DIgR2 is a functionally inhibitory receptor and can mediate negative signaling to regulate DC-initiated antigen-specific T-cell responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Can, S. Tahara-Hanaoka, K. Hitomi, T. Nakano, C. Nakahashi-Oda, N. Kurita, S.-i. Honda, K. Shibuya, and A. Shibuya Caspase-Independent Cell Death by CD300LF (MAIR-V), an Inhibitory Immunoglobulin-Like Receptor on Myeloid Cells J. Immunol., January 1, 2008; 180(1): 207 - 213. [Abstract] [Full Text] [PDF] R. J. Lebbink, T. de Ruiter, G. J. A. Kaptijn, D. G. Bihan, C. A. Jansen, P. J. Lenting, and L. Meyaard Mouse leukocyte-associated Ig-like receptor-1 (mLAIR-1) functions as an inhibitory collagen-binding receptor on immune cells Int. Immunol., August 16, 2007; (2007) dxm071v1. [Abstract] [Full Text] [PDF] J.-S. Chung, K. Sato, I. I. Dougherty, P. D. Cruz Jr, and K. Ariizumi DC-HIL is a negative regulator of T lymphocyte activation Blood, May 15, 2007; 109(10): 4320 - 4327. [Abstract] [Full Text] [PDF] D. Alvarez-Errico, J. Sayos, and M. Lopez-Botet The IREM-1 (CD300f) Inhibitory Receptor Associates with the p85{alpha} Subunit of Phosphoinositide 3-Kinase J. Immunol., January 15, 2007; 178(2): 808 - 816. [Abstract] [Full Text] [PDF]

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