House Dust Mites Activate Nociceptor-mast Cell Clusters to Drive Type 2 Skin Inflammation

Overview

Journal Nat Immunol

Date 2019 Oct 9

PMID 31591569

Citations 125

Authors

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

Affiliations

Soon will be listed here.

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 TRPV1Tac1 nociceptor-MRGPRB2 mast cell sensory clusters represents a key early event in the development of allergic skin reactions.

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