Emerging roles and therapeutic implications of HDAC2 and IL-17A in steroid-resistant asthma

Steroid resistance represents a major clinical problem in the treatment of severe asthma,and therefore a better understanding of its pathogenesis is warranted.Recent studies indicated that histone deacetylase 2(HDAC2)and interleukin 17A(IL-17A)play important roles in severe asthma.HDAC2 activity is reduced in patients with severe asthma and smoking-induced asthma,perhaps accounting for the amplified expression of inflammatory genes,which is associated with increased acetylation of glucocorticoid receptors.Neutrophilic inflammation contributes to severe asthma and may be related to T helper(Th)17 rather than Th2 cytokines.IL-17A levels are elevated in severe asthma and correlate with the presence of neutrophils.Restoring the activity of HDAC2 or targeting the Th17 signaling pathway is a potential therapeutic approach to reverse steroid insensitivity.