Roles of HDACs in the responses of innate immune cells and as targets in inflammatory diseases

Abstract

Histone deacetylases (HDACs) are an emerging class of molecules involved in the epigenetic regulation of innate immune responses through Toll-like receptor (TLR) and interferon (IFN) signaling pathways. HDACs are also key drivers of inflammatory diseases via epigenetic regulation through chromatin DNA and histone modification by methylation and acetylation, among other mechanisms, which control innate immune cell gene expression. Importantly, these epigenetic changes are reversible, and HDACs may also be targeted by small-molecule HDAC inhibitors, which have been used in clinical settings for cancer therapy. Here, we highlight HDACs as strong therapeutic molecules and explore HDAC-induced mechanisms regulating innate immune responses and inflammatory cytokine control, with the goal of developing personalized medicine for the treatment of human diseases, including inflammatory diseases and immune disorders. Currently, this novel class of immunomodulatory therapeutics is being evaluated in the laboratory, in preclinical models, and in the clinic.