Canonical TH2-associated cytokines such as interleukin-4 (IL-4) and IL-13 directly modulate neuronal responses resulting in itch or pain sensitization. Our objective was to highlight the importance of IL-13Rα1 signaling in itch and other neuronal mechanisms. To study these phenomena, we used eblasakimab, a monoclonal human IgG4 antibody that binds to the human type-2 receptor subunit IL-13Rα1 with high affinity. Eblasakimab prevents signaling of IL-4 and IL-13 through IL-13Rα1 on a variety of different cell types. Using an ex-vivo human neuronal model system, human dorsal root ganglia (hDRG) neurons in culture were treated with IL-4 or IL-13 and subsequently subjected to pruritogens. Neuronal responses were captured by live cell calcium imaging. In addition, we measured neuronal spontaneous activity (SA) induced by IL-4 and IL-13 alone or in combination with inflammatory soup (IS). Our data with human sensory neurons pre-stimulated with IL-4, IL-13, or their combination showed a neuronal enhancer effect with no obvious synergy on pruritic pathways or spontaneous activity. Eblasakimab significantly reduced the sensitized responses to bovine adrenal medulla 8–22 peptide (BAM8-22) by up to 80% compared to control conditions (p = 0.02). In addition, IL-13 sensitized hDRG neurons to pro-adrenomedullin peptide 1-20 (PAMP20), a ligand of the itch-specific Mas-related G-protein coupled receptor X2 (MRGPRX2), demonstrating that the itch receptor is functional in human sensory neurons. Our data on SA showed that IL-4 directly induced spontaneous activity as well as enhanced IS induced inflammatory activity in DRG neurons. Both enhancement effects of IL-4 were reduced by eblasakimab. Thus, signaling through Type 2 receptor may result in neuronal amplification for a wide range of itch pathways and expand on neuromodulation beyond itch, and these may be targeted by eblasakimab.

LB061 - Insight into novel itch pathways and spontaneous neuronal activity by targeting interleukin-13 receptor alpha 1 (IL-13Rα1) with eblasakimab

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.