Poly‐ ADP ribose polymerase‐14 limits severity of allergic skin disease

Summary Poly‐ ADP ribose polymerase‐14 ( PARP 14 or ARTD 8) was initially identified as a transcriptional co‐activator for signal transducer and activator of transcription 6 (Stat6), where the presence of interleukin‐4 ( IL ‐4) and activated Stat6 induces the enzymatic activity of PARP 14 that promotes T helper type 2 differentiation and allergic airway disease. To further our understanding of PARP 14 in allergic disease, we studied the function of PARP 14 in allergic inflammation of skin using mice that express constitutively active Stat6 in T cells (Stat6 VT ) and develop spontaneous inflammation of the skin. We mated Stat6 VT mice to Parp14 −/− mice and observed that approximately 75% of the Stat6 VT × Parp14 −/− mice develop severe atopic dermatitis ( AD )‐like lesions, compared with about 50% of Stat6 VT mice, and have increased morbidity compared with Stat6 VT mice. Despite this, gene expression in the skin and the cellular infiltrates was only modestly altered by the absence of PARP 14. In contrast, we saw significant changes in systemic T‐cell cytokine production. Moreover, adoptive transfer experiments demonstrated that decreases in IL ‐4 production reflected a cell intrinsic role for PARP 14 in Th2 cytokine control. Hence, our data suggest that although PARP 14 has similar effects on T‐cell cytokine production in several allergic disease models, the outcome of those effects is distinct, depending on the target organ of disease.