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The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance.

Villagra, Alejandro and Cheng, Fengdong and Wang, Hong-Wei and Suarez, Ildelfonso and Glozak, Michelle and Maurin, Michelle and Nguyen, Danny and Wright, Kenneth L and Atadja, Peter and Bhalla, Kapil and Pinilla-Ibarz, Javier and 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
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
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Date Deposited: 14 Dec 2009 13:48
Last Modified: 31 Jan 2013 00:53
URI: https://oak.novartis.com/id/eprint/1524

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