Role of PARP-14 in allergic airway disease

Interleukin-4 (IL-4) and STAT6 play an important role in progression of allergic airway disease (AAD) or asthma.  In T cells IL-4 and STAT6 mediate T helper 2 (Th2) responses that promotes the asthmatic condition, and in B cells immunoglobulin class switching to IgE is dependent on IL-4 and STAT6.  We have demonstrated that PARP-14, a member of the poly ADP-ribose polymerase (PARP) family of proteins regulates STAT6 dependent transcription by functioning as a transcriptional switch.  However, the role of PARP-14 in AAD dependent on airway hyper-responsiveness (AHR) and lung inflammation has not been investigated.  Using a mouse model of AAD we demonstrate that PARP-14 deficient animals when compared to controls show reduced lung pathology and IgE.  Further, treating mice with a pharmacological inhibitor for PARP activity reduced the severity of AHR and lung inflammation.  Mechanistically, our data indicate that PARP-14 and its enzyme activity aid in the differentiation of T cells towards a Th2 phenotype by regulating the binding of STAT6 to the Gata3 promoter.  These results indicate that PARP-14 and the catalytic activity associated with it promote Th2 differentiation and AAD, and targeting PARP-14 may be a potential new therapy for allergic asthma.