Regulation of Immune Responses by Histone Deacetylase Inhibitors

Figure 1

Schematic representation of HDACi immunomodulation. (1) HDACi such as Trichostatin A and SAHA suppress the activity of class I/II HDAC enzymes (2). This reverses the acetylation status, leading to (hyper)acetylation of both (3) histone and (4) nonhistone proteins such as nuclear transcription factors. Together, chromatin remodelling and immune gene expression is altered and, in the context of the immune system, can lead to immunomodulation (5). Among the pleiotropic activities of HDACi, activation of Treg cells limits the extent of inflammatory-mediated tumourigenesis as well as the development of Th17 cells. HDACi also directly inhibit the activity of Th1 cells mainly by repression of the Th2 regulator, GATA-3. Inhibition of proinflammatory APC function is also mediated by HDACi by modulating NF-κB activation status. These properties of HDACi are also important in the immunosurveillance of cancer by upregulating specific markers that enhance tumour antigenicity and targeted immune system-mediated cytotoxicity CD8+ T cells and NK cells.