Liu Andrew W, Zhang Youran R, Chen Chien-Sin, Edwards Tara N, Ozyaman Sumeyye, Ramcke Torben, McKendrick Lindsay M, Weiss Eric S, Gillis Jacob E, Laughlin Colin R, Randhawa Simran K, Phelps Catherine M, Kurihara Kazuo, Kang Hannah M, Nguyen Sydney-Lam N, Kim Jiwon, Sheahan Tayler D, Ross Sarah E, Meisel Marlies, Sumpter Tina L, Kaplan Daniel H
Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
Science. 2025 Jan 31;387(6733):eadn9390. doi: 10.1126/science.adn9390.
Itch is a dominant symptom in dermatitis, and scratching promotes cutaneous inflammation, thereby worsening disease. However, the mechanisms through which scratching exacerbates inflammation and whether scratching provides benefit to the host are largely unknown. We found that scratching was required for skin inflammation in mouse models dependent on FcεRI-mediated mast cell activation. Scratching-induced inflammation required pain-sensing nociceptors, the neuropeptide substance P, and the mast cell receptor MrgprB2. Scratching also increased cutaneous inflammation and augmented host defense to superficial infection. Thus, through the activation of nociceptor-driven neuroinflammation, scratching both exacerbated allergic skin disease and provided protection from , reconciling the seemingly paradoxical role of scratching as a pathological process and evolutionary adaptation.
瘙痒是皮炎的主要症状，搔抓会促进皮肤炎症，从而使病情恶化。然而，搔抓加剧炎症的机制以及搔抓是否对宿主有益在很大程度上尚不清楚。我们发现，在依赖FcεRI介导的肥大细胞活化的小鼠模型中，皮肤炎症需要搔抓。搔抓诱导的炎症需要痛觉感受器、神经肽P物质和肥大细胞受体MrgprB2。搔抓还会增加皮肤炎症，并增强宿主对浅表感染的防御能力。因此，通过激活伤害感受器驱动的神经炎症，搔抓既加剧了过敏性皮肤病，又提供了对……的保护，调和了搔抓作为病理过程和进化适应这一看似矛盾的作用。
