Brogdon, Jennifer, Xu, Yongyao, Szabo, Susanne, An, Shaojian, Buxton, Francis, Cohen, Dalia and Huang, Qian (2007) Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function. Blood, 109 (3). pp. 1123-1130. ISSN 0006-4971

Abstract

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.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Additional Information:	free final full text version available at publisher's official URL author can archive post-print (ie final draft post-refereeing), but Cannot archive until publication;
Keywords:	http://bloodjournal.hematologylibrary.org/cgi/content/full/109/3/1123
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 14:07
Last Modified:	14 Dec 2009 14:07
URI:	https://oak.novartis.com/id/eprint/23