FcεR1-expressing nociceptors trigger allergic airway inflammation.
Allergens
/ immunology
Animals
Calcium
/ metabolism
Disease Models, Animal
Disease Susceptibility
/ immunology
Gene Expression
Genetic Predisposition to Disease
Hypersensitivity
/ genetics
Mice
Mice, Knockout
Neurons
/ immunology
Nociceptors
/ metabolism
Ovalbumin
/ adverse effects
Receptors, IgE
/ genetics
Respiratory Mucosa
/ immunology
Substance P
/ metabolism
Vagus Nerve
FcεR1
Neuroimmunity
T(H)2
TRPV1
allergen detection
allergy
asthma
nociceptor neurons
substance P
vagal sensing
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
13
05
2020
revised:
12
12
2020
accepted:
17
12
2020
pubmed:
17
1
2021
medline:
5
10
2021
entrez:
16
1
2021
Statut:
ppublish
Résumé
Lung nociceptor neurons amplify immune cell activity and mucus metaplasia in response to an inhaled allergen challenge in sensitized mice. We sought to identify the cellular mechanisms by which these sensory neurons are activated subsequent to allergen exposure. We used calcium microscopy and electrophysiologic recording to assess whether vagal neurons directly respond to the model allergen ovalbumin (OVA). Next, we generated the first nociceptor-specific FcεR1γ knockdown (TRPV1 Lung-innervating jugular nodose complex ganglion neurons express the high-affinity IgE receptor FcεR1, the levels of which increase in OVA-sensitized mice. FcεR1γ-expressing vagal nociceptor neurons respond directly to OVA complexed with IgE with depolarization, action potential firing, calcium influx, and neuropeptide release. Activation of vagal neurons by IgE-allergen immune complexes, through the release of substance P from their peripheral terminals, directly amplifies T Allergen sensitization triggers a feedforward inflammatory loop between IgE-producing plasma cells, FcεR1-expressing vagal sensory neurons, and T
Sections du résumé
BACKGROUND
Lung nociceptor neurons amplify immune cell activity and mucus metaplasia in response to an inhaled allergen challenge in sensitized mice.
OBJECTIVE
We sought to identify the cellular mechanisms by which these sensory neurons are activated subsequent to allergen exposure.
METHODS
We used calcium microscopy and electrophysiologic recording to assess whether vagal neurons directly respond to the model allergen ovalbumin (OVA). Next, we generated the first nociceptor-specific FcεR1γ knockdown (TRPV1
RESULTS
Lung-innervating jugular nodose complex ganglion neurons express the high-affinity IgE receptor FcεR1, the levels of which increase in OVA-sensitized mice. FcεR1γ-expressing vagal nociceptor neurons respond directly to OVA complexed with IgE with depolarization, action potential firing, calcium influx, and neuropeptide release. Activation of vagal neurons by IgE-allergen immune complexes, through the release of substance P from their peripheral terminals, directly amplifies T
CONCLUSIONS
Allergen sensitization triggers a feedforward inflammatory loop between IgE-producing plasma cells, FcεR1-expressing vagal sensory neurons, and T
Identifiants
pubmed: 33453289
pii: S0091-6749(21)00008-7
doi: 10.1016/j.jaci.2020.12.644
pmc: PMC9004488
mid: NIHMS1662693
pii:
doi:
Substances chimiques
Allergens
0
Receptors, IgE
0
Substance P
33507-63-0
Ovalbumin
9006-59-1
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2330-2342Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL130540
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS039518
Pays : United States
Organisme : CIHR
ID : 407016
Pays : Canada
Organisme : CIHR
ID : 136802
Pays : Canada
Organisme : NICHD NIH HHS
ID : P30 HD018655
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL122531
Pays : United States
Informations de copyright
Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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