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- Title
The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance.
- Authors
Villagra, Alejandro; Cheng, Fengdong; Wang, Hong-Wei; Suarez, Ildelfonso; Glozak, Michelle; Maurin, Michelle; Nguyen, Danny; Wright, Kenneth L; Atadja, Peter W; Bhalla, Kapil; Pinilla-Ibarz, Javier; Seto, Edward; Sotomayor, Eduardo M
- 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.
- Publication
Nature immunology, 2009, Vol 10, Issue 1, p92
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.1673