Journal Club- 21/1/2009 CIMR

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

Alejandro Villagra1, Fengdong Cheng1, Hong-Wei Wang1, Ildelfonso Suarez1,2, Michelle Glozak3,4, Michelle Maurin1, Danny Nguyen1, Kenneth L Wright1,4, Peter W Atadja5, Kapil Bhalla6, Javier Pinilla-Ibarz1,4, Edward Seto3,4 & Eduardo M Sotomayor1,3,4

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.