SEARCH:   Advanced

Blood, 1 February 2007, Vol. 109, No. 3, pp. 1123-1130. Prepublished online as a Blood First Edition Paper on September 28, 2006; DOI 10.1182/blood-2006-04-019711. This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: blood-2006-04-019711v1 109/3/1123    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 Brogdon, J. L. Articles by Huang, Q. Search for Related Content PubMed PubMed Citation Articles by Brogdon, J. L. Articles by Huang, Q. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function Jennifer L. Brogdon1, Yongyao Xu1, Susanne J. Szabo1, Shaojian An2, Francis Buxton2, Dalia Cohen2, and Qian Huang1 1 Department of Developmental & Molecular Pathways, Novartis Institute for BioMedical Research (NIBR), Cambridge, MA; and 2 Department of Genome and Proteome Sciences, NIBR, Cambridge, MA Histone deacetylases (HDACs) play a critical role in regulating gene expression and key biological processes. However, how HDACs are involved in innate immunity is little understood. Here, in this first systematic investigation of the role of HDACs in immunity, we show that HDAC inhibition by a small-molecule HDAC inhibitor (HDACi), LAQ824, alters Toll-like receptor 4 (TLR4)–dependent activation and function of macrophages and dendritic cells (DCs). Surprisingly, pan-HDAC inhibition modulates only a limited set of genes involved in distinct arms of immune responses. Specifically, it inhibited DC-controlled T helper 1 (Th1) effector but not Th2 effector cell activation and migration. It also inhibited macrophage- and DC-mediated monocyte but not neutrophil chemotaxis. These unexpected findings demonstrate the high specificity of HDAC inhibition in modulating innate and adaptive immune responses, and highlight the potential for HDACi to alter the Th1 and Th2 balance in therapeutic settings. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. D. Vo, R. M. Prins, J. L. Begley, T. R. Donahue, L. F. Morris, K. W. Bruhn, P. de la Rocha, M.-Y. Yang, S. Mok, H. J. Garban, et al. Enhanced Antitumor Activity Induced by Adoptive T-Cell Transfer and Adjunctive Use of the Histone Deacetylase Inhibitor LAQ824 Cancer Res., November 15, 2009; 69(22): 8693 - 8699. [Abstract] [Full Text] [PDF] J. M. Gardner, K. G. Evans, S. Goldstein, E. J. Kim, C. C. Vittorio, and A. H. Rook Vorinostat for the Treatment of Bullous Pemphigoid in the Setting of Advanced, Refractory Cutaneous T-Cell Lymphoma Arch Dermatol, September 1, 2009; 145(9): 985 - 988. [Full Text] [PDF] D. S. Schrump Cytotoxicity Mediated by Histone Deacetylase Inhibitors in Cancer Cells: Mechanisms and Potential Clinical Implications Clin. Cancer Res., June 15, 2009; 15(12): 3947 - 3957. [Abstract] [Full Text] [PDF] Y. Sun, Y. E. Chin, E. Weisiger, C. Malter, I. Tawara, T. Toubai, E. Gatza, P. Mascagni, C. A. Dinarello, and P. Reddy Cutting Edge: Negative Regulation of Dendritic Cells through Acetylation of the Nonhistone Protein STAT-3 J. Immunol., May 15, 2009; 182(10): 5899 - 5903. [Abstract] [Full Text] [PDF] S. Chang, P. L. Collins, and T. M. Aune T-Bet Dependent Removal of Sin3A-Histone Deacetylase Complexes at the Ifng Locus Drives Th1 Differentiation J. Immunol., December 15, 2008; 181(12): 8372 - 8381. [Abstract] [Full Text] [PDF] D. Bosisio, M. Vulcano, A. Del Prete, M. Sironi, V. Salvi, L. Salogni, E. Riboldi, F. Leoni, C. A. Dinarello, G. Girolomoni, et al. Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo J. Leukoc. Biol., December 1, 2008; 84(6): 1540 - 1548. [Abstract] [Full Text] [PDF] C. Sebastian, M. Serra, A. Yeramian, N. Serrat, J. Lloberas, and A. Celada Deacetylase Activity Is Required for STAT5-Dependent GM-CSF Functional Activity in Macrophages and Differentiation to Dendritic Cells J. Immunol., May 1, 2008; 180(9): 5898 - 5906. [Abstract] [Full Text] [PDF] N. Li, D. Zhao, M. Kirschbaum, C. Zhang, C.-L. Lin, I. Todorov, F. Kandeel, S. Forman, and D. Zeng HDAC inhibitor reduces cytokine storm and facilitates induction of chimerism that reverses lupus in anti-CD3 conditioning regimen PNAS, March 25, 2008; 105(12): 4796 - 4801. [Abstract] [Full Text] [PDF] M. Dokmanovic, C. Clarke, and P. A. Marks Histone Deacetylase Inhibitors: Overview and Perspectives Mol. Cancer Res., October 1, 2007; 5(10): 981 - 989. [Abstract] [Full Text] [PDF] A. Nencioni, J. Beck, D. Werth, F. Grunebach, F. Patrone, A. Ballestrero, and P. Brossart Histone Deacetylase Inhibitors Affect Dendritic Cell Differentiation and Immunogenicity Clin. Cancer Res., July 1, 2007; 13(13): 3933 - 3941. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020