The role of OSMRβ in inflammatory skin diseases

OSMRβ is a member of the IL-6 cytokine receptor family and plays a critical role in pruritus and immune-mediated skin diseases. Upon inflammatory stimulation, skin immune cells release OSM and IL-31. These cytokines signal through the heterodimeric receptor complexes OSMRβ/gp130 (type II OSM receptor) and OSMRβ/IL-31RA (IL-31 receptor), which are expressed on keratinocytes, fibroblasts, and dorsal root ganglion (DRG) neurons. Engagement of these receptors activates downstream JAK/STAT, MAPK/ERK and PI3K/AKT signaling cascades, leading to itch and inflammation that contributing to the pathogenesis of atopic dermatitis (AD), psoriasis (PSO), prurigo nodularis (PN) and familial primary localized cutaneous amyloidosis (FPLCA). Although a wide range of therapeutic options exist for these diseases, specific targeted treatments remain lacking. Vixarelimab, an OSMRβ-targeting monoclonal antibody, is currently under clinical evaluation for PN and AD.