House dust mites activate nociceptor–mast cell clusters to drive type 2 skin inflammation

Nadine Serhan, Lilian Basso, Riccardo Sibilano, Camille Petitfils, James Meixiong, Chrystelle Bonnart, Laurent L. Reber, Thomas Marichal, Philipp Starkl, Nicolas Cenac, Xinzhong Dong, Mindy Tsai, Stephen J. Galli, Nicolas Gaudenzio

Research output: Contribution to journalArticle

Abstract

Allergic skin diseases, such as atopic dermatitis, are clinically characterized by severe itching and type 2 immunity-associated hypersensitivity to widely distributed allergens, including those derived from house dust mites (HDMs). Here we found that HDMs with cysteine protease activity directly activated peptidergic nociceptors, which are neuropeptide-producing nociceptive sensory neurons that express the ion channel TRPV1 and Tac1, the gene encoding the precursor for the neuropeptide substance P. Intravital imaging and genetic approaches indicated that HDM-activated nociceptors drive the development of allergic skin inflammation by inducing the degranulation of mast cells contiguous to such nociceptors, through the release of substance P and the activation of the cationic molecule receptor MRGPRB2 on mast cells. These data indicate that, after exposure to HDM allergens, activation of TRPV1+Tac1+ nociceptor–MRGPRB2+ mast cell sensory clusters represents a key early event in the development of allergic skin reactions.

Original languageEnglish (US)
Pages (from-to)1435-1443
Number of pages9
JournalNature Immunology
Volume20
Issue number11
DOIs
StatePublished - Nov 1 2019

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Serhan, N., Basso, L., Sibilano, R., Petitfils, C., Meixiong, J., Bonnart, C., Reber, L. L., Marichal, T., Starkl, P., Cenac, N., Dong, X., Tsai, M., Galli, S. J., & Gaudenzio, N. (2019). House dust mites activate nociceptor–mast cell clusters to drive type 2 skin inflammation. Nature Immunology, 20(11), 1435-1443. https://doi.org/10.1038/s41590-019-0493-z