Interleukin-15 (IL-15), a cytokine that regulates among others, immune responses and keratinocyte apoptosis, is reported to be up-regulated in the skin from atopic dermatitis (AD) patients. However, its role in AD development remains unknown. Here, we attempted to explore the contribution of IL-15 in AD by investigating if IL-15 inhibition can prevent and/or counteract the development of experimentally induced AD lesions in a novel humanized model of AD, characterized by skin barrier impairment and a Th2-dependent disease pattern aided by Th1/17/22 cytokines. Skin from healthy donors (n=3) was xenotransplanted onto SCID mice and injected with autologous, in vitro-stimulated PBMCs with IL-4/IL-2/LPS. A monoclonal antibody against IL-15 (CALY-002), a monoclonal antibody blocking IL-4Rα (Dupilumab), or IgG controls were administered intravenously either in a prophylactic or therapeutic setting. A significant up-regulation of IL-15 and IL-15RA expression in the epidermis, and positive cell number in the papillary dermis was confirmed in AD xenotransplants. Both prophylactic and therapeutic IL-15 blockage ameliorated clinical disease signs, and skin barrier integrity, as shown by significant increase of Filaggrin expression, reduction of epidermal thickness, and epidermal keratinocyte proliferation, similarly to Dupilumab, when compared to IgG treatment. Unlike dupilumab, IL-15 inhibition did not prevent or rescue skin xenotranplants from the up-regulation of CD3+ T-cells, but comparably blocked the increase in NK (tendential), IFN+ (significant) and IL-4+ (tendential) cells. IL-15 blockade, though less efficiently than dupilumab, also led to the prevention/rescue of IL-15+, IL-17+, and IL-22+ cells up-regulation in PBMCs injected xenotransplants. Thus, our data further support a role of IL-15 in AD pathogenesis, and encourage the targeting of IL-15 signalling as adjuvant strategy for AD management.

LB053 - Interleukin-15 inhibition ameliorates atopic dermatitis lesions experimentally induced in xenotransplanted human skin

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.