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

Alejandro Villagra, Fengdong Cheng, Hong Wei Wang, Ildelfonso Suarez, Michelle Glozak, Michelle Maurin, Danny Nguyen, Kenneth L. Wright, Peter W. Atadja, Kapil Bhalla, Javier Pinilla-Ibarz, Edward Seto, Eduardo M. Sotomayor

Research output: Contribution to journalArticle

286 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)92-100
Number of pages9
JournalNature immunology
Volume10
Issue number1
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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