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

Allergic skin diseases, such as atopic dermatitis (AD), 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 direct...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858877/
https://www.ncbi.nlm.nih.gov/pubmed/31591569
http://dx.doi.org/10.1038/s41590-019-0493-z
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author 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
author_facet 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
author_sort Serhan, Nadine
collection PubMed
description Allergic skin diseases, such as atopic dermatitis (AD), 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 expressed the ion channel TRPV1 and Tac1, the gene encoding the precursor for the neuropeptide substance P. Intravital imaging and genetic approaches indicated that HDMs-activated nociceptors drove 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 molecules receptor MRGPRB2 on mast cells. This data indicates that, after exposure to HDM allergens, activation of TRPV1(+)Tac1(+) nociceptor-MRGPRB2(+) sensory clusters represents a key early event in the development of allergic skin reaction.
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spelling pubmed-68588772020-04-07 House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation 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 Nat Immunol Article Allergic skin diseases, such as atopic dermatitis (AD), 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 expressed the ion channel TRPV1 and Tac1, the gene encoding the precursor for the neuropeptide substance P. Intravital imaging and genetic approaches indicated that HDMs-activated nociceptors drove 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 molecules receptor MRGPRB2 on mast cells. This data indicates that, after exposure to HDM allergens, activation of TRPV1(+)Tac1(+) nociceptor-MRGPRB2(+) sensory clusters represents a key early event in the development of allergic skin reaction. 2019-10-07 2019-11 /pmc/articles/PMC6858877/ /pubmed/31591569 http://dx.doi.org/10.1038/s41590-019-0493-z Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
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
House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation
title House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation
title_full House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation
title_fullStr House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation
title_full_unstemmed House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation
title_short House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation
title_sort house dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858877/
https://www.ncbi.nlm.nih.gov/pubmed/31591569
http://dx.doi.org/10.1038/s41590-019-0493-z
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