| First Author | Kamiya S | Year | 2022 |
| Journal | J Invest Dermatol | PubMed ID | 35850207 |
| Mgi Jnum | J:328110 | Mgi Id | MGI:7334593 |
| Doi | 10.1016/j.jid.2022.06.021 | Citation | Kamiya S, et al. (2022) Functional Interplay between IL-9 and Peptide YY Contributes to Chronic Skin Inflammation. J Invest Dermatol |
| abstractText | Complex interactions between keratinocytes and various cell types, such as inflammatory cells and stromal cells, contribute to the pathogenesis of chronic inflammatory skin lesions. In proinflammatory cytokinemediated disease settings, IL-9 plays a pathological role in inflammatory dermatitis. However, IL-9related mechanisms remain incompletely understood. In this study, we established tamoxifen-induced keratinocyte-specific IL-9RA-deficient mice (K14(CRE/ERT)Il9ra(Delta/Delta) mice) to examine the role of IL-9 in multicellular interactions under chronic skin inflammatory conditions. Studies using an imiquimod-induced psoriasis-like model showed that K14(CRE/ERT)Il9ra(Delta/Delta) mice exhibited a significantly reduced severity of dermatitis and mast cell infiltration compared with control K14(WT)Il9ra(fl/fl) mice. Transcriptome analyses of psoriasis-like lesions showed that the level of peptide Y-Y (Pyy), a member of the neuropeptide Y family, was markedly downregulated in K14(CRE/ERT)Il9ra(Delta/Delta) epidermis. Pyy blockade suppressed epidermal thickening and mast cell numbers in imiquimod-treated wild-type mice. Together with in vitro studies indicating that Pyy induced IL-9 production and chemotactic activity in bone marrowderived mast cells, these findings suggest that Pyy-mediated interplay between keratinocytes and mast cells contributes to psoriasiform inflammation. Further investigation focusing on the IL-9Pyy axis may provide valuable information for the development of new treatment modalities for inflammatory dermatitis. |
