CpG oligodeoxynucleotides attenuate RORγt-mediated Th17 response by restoring histone deacetylase-2 in cigarette smoke-exposure asthma

Abstract Background Cigarette smoke (CS) exposure increases corticosteroid insensitive asthma related to increased Th17 phenotype, and new treatment strategies are needed for CS-associated asthma. Histone deacetylase 2 (HDAC2), found in the airway epithelium, is critical ameliorating glucocorticoids insensitivity. We recently demonstrated anti-inflammatory effects of CpG oligodeoxynucleotides (CpG-ODNs) on CS-exposure However, CpG-ODNs HDAC2 expression enzymatic activity remain unclear. This study aimed assess whether protect against excessive immune responses CS-induced through HDAC2-dependent mechanisms compared their with those corticosteroids. Methods The alone combination budesonide (BUD) inflammation Th2/Th17-related were determined using an vivo model cultured bronchial epithelial (HBE) cells administered ovalbumin (OVA) and/or cigarette extract (CSE). retinoid-related orphan nuclear receptor γt (RORγt) also assessed mouse lung specimens HBE cells. Results BUD synergistically attenuated CS asthmatic by modulating influx eosinophils neutrophils, remodeling, Th2/Th17 associated cytokine chemokine production, hyperresponsiveness blocking RORγt-mediated induced expression/activity. In vitro , synergized inhibit production OVA- CSE-challenged while suppressing RORγt increasing Conclusions reversed downregulation enhanced sensitivity CS-exposed mice CSE-induced glucocorticoid treatment. effect may be restoration via RORγt/IL-17 pathway regulation, suggesting that potential corticosteroid-sparing agents use Th17-biased conditions.