In this study, we demonstrate that the genetic deletion or depletion of PARP2 has a protective effect against psoriasis-like inflammation in the IMQ-induced murine model and in human keratinocyte cultures and that this protection is dependent on aromatase function and estradiol synthesis, and estradiol-mediated suppression of NF-κB activity in keratinocytes. This evidence concerns the gene PARP2 and psoriasis.