Submitted April 25, 2006
Accepted September 6, 2006
Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function
Jennifer Brogdon, Yongyao Xu, Susanne Szabo, Shaojian An, Francis Buxton, Dalia Cohen, and Qian Huang*
Novartis Institute for Biomedical Research
* Corresponding author; email: qian.huang{at}novartis.com.
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 TLR4-dependent activation and function of macrophages and dendritic cells (DC). Surprisingly, pan HDAC inhibition modulates only a limited set of genes involved in distinct arms of immune responses. Specifically, it inhibited DC-controlled 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.
