HDAC2 attenuates airway inflammation by suppressing IL17A production in HDM-challenged mice.

Histone deacetylase (HDAC) 2 is expressed in airway epithelium and plays a pivotal role in inflammatory cells. However, the role of HDAC2 in allergic airway inflammation remains poorly unknown. In the present study, we determined the role of HDAC2 in airway inflammation using in vivo models of HDM-induced allergic inflammation and in vitro cultures of human bronchial epithelial (HBE) cells exposed to HDM, IL17A, or both. We observed that HDM-challenged Hdac2+/- mice exhibited substantially enhanced infiltration of inflammatory cells. Higher levels of Th2 cytokines and IL17A expression were found in lung tissues of HDM-challenged Hdac2+/- mice. Interestingly, IL17A deletion or anti-IL17A treatment reversed the enhanced airway inflammation induced by HDAC2 impairment. In vitro, HDM and IL17A synergistically decreased HDAC2 expression in HBE cells. HDAC2 gene silencing further enhanced HDM- and/or IL17A-induced inflammatory cytokines in HBE cells. HDAC2 overexpresion or blocking IL17A gene expression restored the enhanced inflammatory cytokines. Collectively, these results support a protective role of HDAC2 in HDM-induced airway inflammation by suppressing IL17A production and might suggest that activation of HDAC2 and/or inhibition of IL17A production could prevent the development of allergic airway inflammation.