Low concentrations of histone deacetylase (HDAC) inhibitors have immunomodulatory effects, but their mechanism of action is unclear. This paper showed that the clinically used HDAC inhibitors vorinostat and givinostat protected against the development of type 1 diabetes in a mouse model by increasing the numbers of regulatory T cells and decreasing the numbers of inflammatory dendritic cells and cytokines. Further work showed that these effects were probably mediated through HDAC inhibitor-mediated hyperacetylation of transcription factors, rather than hyperacetylation of nuclear histones.