Scratching promotes allergic inflammation and host defense via neurogenic mast cell activation
成果类型：
Article
署名作者：
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.
署名单位：
Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Istanbul Medipol University; Yale University; Medical College of Wisconsin
刊物名称：
SCIENCE
ISSN/ISSBN：
0036-8909
DOI：
10.1126/science.adn9390
发表日期：
2025-01-31
关键词：
tumor-necrosis-factor
contact hypersensitivity
staphylococcus-aureus
neutrophil recruitment
skin microbiome
dendritic cells
sensory neurons
factor-alpha
mouse
ige
摘要：
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 Fc epsilon RI-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 Staphylococcus aureus infection. Thus, through the activation of nociceptor-driven neuroinflammation, scratching both exacerbated allergic skin disease and provided protection from S. aureus, reconciling the seemingly paradoxical role of scratching as a pathological process and evolutionary adaptation.