Expression data from keratinocyte-specific Zfp36-deficient mouse skin treated with imiquimod

Tristetraprolin (TTP, encoded by Zfp36) regulates the mRNA stability of several important cytokines. Due to the critical role of this RNA-binding protein in the control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL-23 by myeloid cells such as macrophages or dendritic cells. Here, we generated mice with conditional deletion of TTP in keratinocytes. These mice developed exacerbated inflammation in the imiquimod-induced psoriasis model. Furthermore, these mice progressively developed a spontaneous pathology with systemic inflammation, psoriatic-like skin lesions and dactylitis. Finally, we provide evidence that keratinocyte-derived TNF productin drives the different pathological features. In summary, these findings expand current views on the initiation of psoriasis and related arthritis by revealing the keratinocyte-intrinsic role of TTP. Mice with a specific deletion of Zfp36 in keratinocytes and their littermate control were topically treated or not with imiquimod during 5 consecutive days (5 animals by group). 4h after the last application, skins from abdomen were sampled and prepared for RNA extraction and hybridization on Affymetrix microarrays.