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

2019; Nature Portfolio; Volume: 20; Issue: 11 Linguagem: Inglês

10.1038/s41590-019-0493-z

1529-2916

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

Food Allergy and Anaphylaxis Research

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. Gaudenzio and colleagues show that house dust mite extracts directly activate TRPV1+ sensory neurons, which promote allergic skin inflammation by inducing the degranulation of mast cells through the release of the neuropeptide substance P and activation of MRGPRB2.