Chronic itch is a major symptom of many inflammatory skin diseases. This type of pruritus is thought to be facilitated by cytokines that activate cutaneous nerve fibers; however, the molecular components and mechanisms involved are poorly understood. We found that the cytokine oncostatin M (OSM) is highly up-regulated in psoriasis, atopic dermatitis, and cutaneous T cell lymphoma, diseases associated with chronic itch. OSM receptor (OSMR) is expressed by itch-selective natriuretic polypeptide B (Nppb) neurons, and single-cell sequencing showed that OSM is mainly produced by dermal T cells and monocytes. Unlike canonical pruritogens, OSM does not activate sensory neurons. Instead, it sensitizes neurons by potentiating neural responses to pruritogens and by enhancing neural excitability. Knockout of OSMR in sensory neurons attenuated OSM-sensitized itch and inflammatory itch in mice, and pharmacological antagonism of the OSMR complex effectively alleviated pruritus in experimental inflammatory dermatitis in a rodent model. Together, our results uncover OSM as an itch neuromodulator and reveal OSM signal transduction as a potential target for antipruritic therapy.

中文翻译：

---

制瘤素 M 可以使炎症性瘙痒的感觉神经元敏感

慢性瘙痒是许多炎症性皮肤病的主要症状。这种类型的瘙痒被认为是由激活皮肤神经纤维的细胞因子促进的。然而，所涉及的分子成分和机制却知之甚少。我们发现细胞因子制瘤素 M (OSM) 在银屑病、特应性皮炎和皮肤 T 细胞淋巴瘤（与慢性瘙痒相关的疾病）中高度上调。OSM受体（OSMR）由瘙痒选择性利钠肽B（Nppb）神经元表达，单细胞测序显示OSM主要由真皮T细胞和单核细胞产生。与典型的瘙痒原不同，OSM 不会激活感觉神经元。相反，它通过增强对瘙痒原的神经反应和增强神经兴奋性来使神经元敏感。敲除感觉神经元中的 OSMR 可减轻小鼠的 OSM 致敏性瘙痒和炎症性瘙痒，OSMR 复合物的药理拮抗作用可有效缓解啮齿动物模型实验性炎症性皮炎的瘙痒。总之，我们的结果揭示了 OSM 作为一种瘙痒神经调节剂，并揭示了 OSM 信号转导作为止痒治疗的潜在目标。