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Serhan, Nadine; Basso, Lilian; Sibilano, Riccardo; Petitfils, Camille; Meixiong, James; Bonnart, Chrystelle; Reber, Laurent L; Marichal, Thomas; Starkl, Philipp; Cenac, Nicolas; Dong, Xinzhong; Tsai, Mindy; Galli, Stephen J; Gaudenzio, Nicolas
Nature immunology, 11/2019, Letnik: 20, Številka: 11Journal Article
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.
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