GSE190867
Next Generation Sequencing  of wild type (WT) and K14 conditional Il9ra-/- mice  ear epidermal cell layers
Complex interactions of keratinocytes with various cells like inflammatory cells and stromal cells contribute to the pathogenesis of chronic inflammatory dermatoses. In proinflammatory cytokines mediating such ill settings, interleukin (IL)-9 plays a pathological role in inflammatory dermatoses. However, IL-9-related mechanisms in such diseases are still incompletely understood. In this study, we established tamoxifen-induced keratinocyte-specific IL-9 receptor alpha-chain-deficient mice (K14CRE/ERTIl9ra?/? mice) to examine the role of IL-9 in multicellular interactions under the condition of chronic skin inflammation. Studies using an imiquimod-induced psoriasis-like model showed that K14CRE/ERTIl9ra?/? mice significantly reduced the severity of dermatitis and mast cell infiltration compared to K14WTIl9rafl/fl mice as controls. The transcriptome analyses of psoriasis-like lesions showed that the level of peptide tyrosine-tyrosine (Pyy), a member of neuropeptide Y family, was markedly downregulated in K14CRE/ERTIl9ra?/? epidermis. Blockade of Pyy suppressed thickening of the epidermis and mast cell number in imiquimod-treated wild-type mice. Together with in vitro studies indicating a capacity of Pyy to induce IL-9 production and chemotactic activity of bone marrow-derived mast cells (BMMCs), these suggest that Pyy-mediated interplay of keratinocytes and mast cells induces psoriasiform inflammation. Further investigation focusing on the IL-9-Pyy axis would provide a new modality for treatment of chronic inflammatory dermatoses. Overall design: Epidermal RNA profiles of IMQ treated wild type (WT) and K14 conditional Il9ra-/- mice