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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 14, 2006 Accepted August 4, 2006 Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-B activation in dendritic cells Pradip Sen, Mark A Wallet, Zuoan Yi, Yingsu Huang, Michael Henderson, Clayton E Mathews, H. Shelton Earp, Glenn Matsushima, Albert S Baldwin Jr., and Roland M Tisch* Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA Lineberger Comprehensive Cancer Center/Department of Medicine and Pharmacology, UNC, Chapel Hill, NC Department of Microbiology and Immunology/Lineberger Comprehensive Center/Neuroscience Center, UNC Lineberger Comprehensive Cancer Center/Department of Biology, UNC, Chapel Hill, NC Department of Microbiology and Immunology/Lineberger Comprehensive Center, UNC, Chapel Hill, NC * Corresponding author; email: rmtisch{at}med.unc.edu. Dendritic cells (DC) play a key role in immune homeostasis and maintenance of self-tolerance. Tolerogenic DC can be established by an encounter with apoptotic cells (AC) and subsequent inhibition of maturation and effector functions. The receptor(s) and signaling pathway(s) involved in AC-induced inhibition of DC 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 AC is required for mediating this effect. Monocyte-derived DC lacking MerTK expression (MerTKKD) or treated with blocking MerTK-specific Ab 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 DC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Yi, L. Li, G. K. Matsushima, H. S. Earp, B. Wang, and R. Tisch A novel role for c-Src and STAT3 in apoptotic cell-mediated MerTK-dependent immunoregulation of dendritic cells Blood, October 8, 2009; 114(15): 3191 - 3198. [Abstract] [Full Text] [PDF] Y. Chen, S. Khanna, C. S. Goodyear, Y. B. Park, E. Raz, S. Thiel, C. Gronwall, J. Vas, D. L. Boyle, M. Corr, et al. Regulation of Dendritic Cells and Macrophages by an Anti-Apoptotic Cell Natural Antibody that Suppresses TLR Responses and Inhibits Inflammatory Arthritis J. Immunol., July 15, 2009; 183(2): 1346 - 1359. [Abstract] [Full Text] [PDF] 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] J. C. Todt, B. Hu, and J. L. Curtis The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages J. Leukoc. Biol., August 1, 2008; 84(2): 510 - 518. [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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