Isoform-Selective HDAC Inhibition in Autoimmune Disease

Histone deacetylases are a class of enzymes that play an important role in protein modification and cellular function. Ongoing research suggests that HDAC inhibitors may be efficacious in the treatment of a wide range of diseases from cancer to autoimmune disease. HDACi therapy has shown promising results both in vitro and in vivo for the treatment of autoimmune disease. To date, 18 isoforms of HDACs have been identified, which exist in four different classes: class I (HDAC1, 2, 3, and 8), class II (HDAC4, 5, 6, 7, 9, and 10) class III (sirtuins1-7), and class IV (HDAC11). The mechanism of action through which HDACs function remains to be fully elucidated. However, the use of isoform-selective HDAC inhibitors has been helpful in determining the physiological role of individual HDACs as well as in decreasing the toxicity of HDACi therapy. This review will focus on isoform-selective HDACs and how they may be effective for the treatment of autoimmune disease.