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

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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

Edité par CCSD ; Nature Publishing Group -

International audience. 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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