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Blood, 15 January 2007, Vol. 109, No. 2, pp. 653-660. Prepublished online as a Blood First Edition Paper on September 28, 2006; DOI 10.1182/blood-2006-04-017368. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-04-017368v1 109/2/653    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 Sen, P. Articles by Tisch, R. M. Search for Related Content PubMed PubMed Citation Articles by Sen, P. Articles by Tisch, R. M. Related Collections Immunobiology Phagocytes Apoptosis Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Apoptotic cells induce Mer tyrosine kinase–dependent blockade of NF-B activation in dendritic cells Pradip Sen1, Mark A. Wallet1, Zuoan Yi1, Yingsu Huang1, Michael Henderson1, Clayton E. Mathews2, H. Shelton Earp3,4, Glenn Matsushima1,3,5, Albert S. Baldwin, Jr3,6, and Roland M. Tisch1,3, 1 Department of Microbiology and Immunology, 3 University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, 4 Department of Medicine and Pharmacology, 5 UNC Neuroscience Center, and 6 Department of Biology, University of North Carolina at Chapel Hill; 2 Department of Pediatrics, University of Pittsburgh, PA Dendritic cells (DCs) play a key role in immune homeostasis and maintenance of self-tolerance. Tolerogenic DCs can be established by an encounter with apoptotic cells (ACs) and subsequent inhibition of maturation and effector functions. The receptor(s) and signaling pathway(s) involved in AC-induced inhibition of DCs have yet to be defined. We demonstrate that pretreatment with apoptotic but not necrotic cells inhibits activation of IB kinase (IKK) and downstream NF-B. Notably, receptor tyrosine kinase Mer (MerTK) binding of ACs is required for mediating this effect. Monocyte-derived DCs lacking MerTK expression (MerTKKD) or treated with blocking MerTK-specific antibodies (Abs) are resistant to AC-induced inhibition and continue to activate NF-B and secrete proinflammatory cytokines. Blocking MerTK activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevents AC-induced inhibition. These results demonstrate an essential role for MerTK-mediated regulation of the PI3K/AKT and NF-B pathways in AC-induced inhibition of monocyte-derived DCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. A. Wallet, R. R. Flores, Y. Wang, Z. Yi, C. J. Kroger, C. E. Mathews, H. S. Earp, G. Matsushima, B. Wang, and R. Tisch MerTK regulates thymic selection of autoreactive T cells PNAS, March 24, 2009; 106(12): 4810 - 4815. [Abstract] [Full Text] [PDF] H. Hemmi, J. Idoyaga, K. Suda, N. Suda, K. Kennedy, M. Noda, A. Aderem, and R. M. Steinman A New Triggering Receptor Expressed on Myeloid Cells (Trem) Family Member, Trem-Like 4, Binds to Dead Cells and Is a DNAX Activation Protein 12-Linked Marker for Subsets of Mouse Macrophages and Dendritic Cells J. Immunol., February 1, 2009; 182(3): 1278 - 1286. [Abstract] [Full Text] [PDF] H. Ait-Oufella, V. Pouresmail, T. Simon, O. Blanc-Brude, K. Kinugawa, R. Merval, G. Offenstadt, G. Leseche, P. L. Cohen, A. Tedgui, et al. Defective Mer Receptor Tyrosine Kinase Signaling in Bone Marrow Cells Promotes Apoptotic Cell Accumulation and Accelerates Atherosclerosis Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1429 - 1431. [Abstract] [Full Text] [PDF] N. Tibrewal, Y. Wu, V. D'mello, R. Akakura, T. C. George, B. Varnum, and R. B. Birge Autophosphorylation Docking Site Tyr-867 in Mer Receptor Tyrosine Kinase Allows for Dissociation of Multiple Signaling Pathways for Phagocytosis of Apoptotic Cells and Down-modulation of Lipopolysaccharide-inducible NF-{kappa}B Transcriptional Activation J. Biol. Chem., February 8, 2008; 283(6): 3618 - 3627. [Abstract] [Full Text] [PDF] C.-Q. Xia, R. Peng, Y. Qiu, M. Annamalai, D. Gordon, and M. J. Clare-Salzler Transfusion of Apoptotic {beta}-Cells Induces Immune Tolerance to {beta}-Cell Antigens and Prevents Type 1 Diabetes in NOD Mice Diabetes, August 1, 2007; 56(8): 2116 - 2123. [Abstract] [Full Text] [PDF]

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