Scratching promotes allergic inflammation and host defense via neurogenic mast cell activation. Science 2025 Jan 31;387(6733):eadn9390
Date
01/30/2025Pubmed ID
39883751Pubmed Central ID
PMC11983162DOI
10.1126/science.adn9390Scopus ID
2-s2.0-85217623703 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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 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.
Author List
Liu AW, Zhang YR, Chen CS, Edwards TN, Ozyaman S, Ramcke T, McKendrick LM, Weiss ES, Gillis JE, Laughlin CR, Randhawa SK, Phelps CM, Kurihara K, Kang HM, Nguyen SN, Kim J, Sheahan TD, Ross SE, Meisel M, Sumpter TL, Kaplan DHAuthor
Tayler D. Sheahan PhD Assistant Professor in the Cell Biology Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDermatitis, Atopic
Disease Models, Animal
Female
Male
Mast Cells
Mice
Mice, Inbred C57BL
Neurogenic Inflammation
Nociceptors
Pruritus
Receptors, G-Protein-Coupled
Receptors, IgE
Receptors, Neuropeptide
Skin
Staphylococcal Skin Infections
Staphylococcus aureus
Substance P
