Villagra, Alejandro, Cheng, Fengdong, Wang, Hong-Wei, Suarez, Ildelfonso, Glozak, Michelle, Maurin, Michelle, Nguyen, Danny, Wright, Kenneth L, Atadja, Peter, Bhalla, Kapil, Pinilla-Ibarz, Javier, Seto, Edward and Sotomayor, Eduardo M (2009) The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nature Immunology, 10 (1). pp. 92-100. ISSN 1529-2916

Abstract

Antigen-presenting cells (APCs) induce T cell activation as well as T cell tolerance. The molecular basis of the regulation of this critical 'decision' is not well understood. Here we show that HDAC11, a member of the HDAC histone deacetylase family with no prior defined physiological function, negatively regulated expression of the gene encoding interleukin 10 (IL-10) in APCs. Overexpression of HDAC11 inhibited IL-10 expression and induced inflammatory APCs that were able to prime naive T cells and restore the responsiveness of tolerant CD4+ T cells. Conversely, disruption of HDAC11 in APCs led to upregulation of expression of the gene encoding IL-10 and impairment of antigen-specific T cell responses. Thus, HDAC11 represents a molecular target that influences immune activation versus immune tolerance, a critical 'decision' with substantial implications in autoimmunity, transplantation and cancer immunotherapy.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 13:48
Last Modified:	31 Jan 2013 00:53
URI:	https://oak.novartis.com/id/eprint/1524