Convergent Oncostatin M and IL-31 Signaling in Chronic Pruritic Dermatoses: A Neuroimmune Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) Perspective.

Chronic pruritus is a common and difficult-to-manage feature of inflammatory skin conditions. It develops through complex interactions between the skin barrier, immune system, and peripheral nervous system. Interleukin-31 (IL-31) and oncostatin M (OSM), both members of the interleukin-6 (IL-6) cytokine family, share the same receptor subunit, OSM receptor β (OSMRβ), and activate common downstream intracellular pathways, particularly the Janus kinase-signal transducer and activator of transcription (JAK-STAT) cascade. This systematic review aims to synthesize evidence in the current literature that supports IL-31 and OSM signaling across chronic pruritic dermatoses, with an emphasis on downstream JAK1-STAT3 pathways. A comprehensive search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, Ovid MEDLINE, and the Web of Science databases. Studies evaluating OSM, IL-31, their shared receptor components (IL-31 receptor A (IL-31RA) and OSMRβ), and downstream intracellular signaling in chronic pruritic dermatoses were included. Twenty-six studies met the eligibility criteria, comprising randomized controlled trials, case-control studies, cross-sectional studies, case series, and experimental laboratory studies. Across atopic dermatitis (AD), prurigo nodularis (PN), psoriasis, cutaneous T-cell lymphoma (CTCL), dermatomyositis, and primary localized cutaneous amyloidosis (PLCA), both IL-31 and OSM contribute to chronic itch through overlapping pathways, including shared receptor architecture and activation of JAK1-STAT3 signaling. They were found to differ, however, in the way they influence neuronal activation and sensitization. IL-31 acts as a direct pruritogenic cytokine through activation of the IL-31RA/OSMRβ receptor complex on sensory neurons. In contrast, OSM may act to increase neuronal sensitivity, enhance excitability, and strengthen the response to other pruritic-inducing stimuli through the gp130/OSMRβ receptor complex. Despite these differences, both cytokines converge on the JAK1-driven STAT3 signaling pathway, ultimately contributing to skin barrier dysfunction, ongoing inflammation, and persistent neural sensitization. Blocking IL-31RA with nemolizumab or targeting OSMRβ with vixarelimab has led to clinically significant improvements in itch severity, patient-reported quality of life, and sleep disturbance. Together, these findings suggest that the shared components of the IL-31 and OSM pathways, including OSMRβ and JAK1-STAT3, provide us with a big picture framework for understanding itch pathogenesis in chronic pruritic dermatoses and may help guide therapeutic strategies in the future.