Here we investigate the role of PARP-14 and the enzyme activity associated with it in a model of AAD dependent on airway hyperresponsiveness and lung inflammation. We also elucidate the mechanism by which PARP-14 regulates AAD.
The role of PARP-14 and its enzyme activity in AAD and TH2 differentiation were examined by using a murine model of AAD and in?vitro TH cell differentiation.
PARP-14-deficient animals show reduced lung pathology and IgE levels when compared with control animals. Treating mice with a pharmacologic inhibitor for PARP activity reduced the severity of airway hyperresponsiveness and lung inflammation. Mechanistically, our data indicate that PARP-14 and its enzyme activity aid in the differentiation of T cells toward a TH2 phenotype by regulating the binding of STAT6 to the Gata3 promoter.
PARP-14 and the catalytic activity associated with?it promote TH2 differentiation and AAD in a murine model, and targeting PARP-14 might be a potential new therapy?for allergic asthma.