Epicutaneous allergen immunotherapy induces a profound and selective modulation in skin dendritic-cell subsets.
Food allergy
T-cell responses
allergen immunotherapy
desensitization
epicutaneous immunotherapy
skin dendritic cells
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:
Nov 2022
Nov 2022
Historique:
received:
21
12
2021
revised:
03
05
2022
accepted:
24
05
2022
pubmed:
3
7
2022
medline:
9
11
2022
entrez:
2
7
2022
Statut:
ppublish
Résumé
Epicutaneous immunotherapy (EPIT) protocols have recently been developed to restore tolerance in patients with food allergy. The mechanisms by which EPIT protocols promote desensitization rely on a profound immune deviation of pathogenic T- and B-cell responses. To date, little is known about the contribution of skin dendritic cells (skDCs) to T-cell remodeling and EPIT efficacy. We capitalized on a preclinical model of food allergy to ovalbumin (OVA) to characterize the phenotype and functions of OVA Our results showed that both Langerhans cells and dermal conventional cDC1 and cDC2 subsets retained their ability to capture OVA in the skin and to migrate toward the skin-draining lymph nodes during EPIT. However, their activation/maturation status was significantly impaired, as evidenced by the gradual and selective reduction of CD86, CD40, and OVA protein expression in respective subsets. Phenotypic changes during EPIT were also characterized by a progressive diversification of single-cell gene signatures within each DC subset. Interestingly, we observed that OVA Our results therefore emphasize that the acquisition of distinct phenotypic and functional specializations by skDCs during EPIT is at the cornerstone of the desensitization process.
Sections du résumé
BACKGROUND
Epicutaneous immunotherapy (EPIT) protocols have recently been developed to restore tolerance in patients with food allergy. The mechanisms by which EPIT protocols promote desensitization rely on a profound immune deviation of pathogenic T- and B-cell responses.
OBJECTIVE
To date, little is known about the contribution of skin dendritic cells (skDCs) to T-cell remodeling and EPIT efficacy.
METHODS
We capitalized on a preclinical model of food allergy to ovalbumin (OVA) to characterize the phenotype and functions of OVA
RESULTS
Our results showed that both Langerhans cells and dermal conventional cDC1 and cDC2 subsets retained their ability to capture OVA in the skin and to migrate toward the skin-draining lymph nodes during EPIT. However, their activation/maturation status was significantly impaired, as evidenced by the gradual and selective reduction of CD86, CD40, and OVA protein expression in respective subsets. Phenotypic changes during EPIT were also characterized by a progressive diversification of single-cell gene signatures within each DC subset. Interestingly, we observed that OVA
CONCLUSIONS
Our results therefore emphasize that the acquisition of distinct phenotypic and functional specializations by skDCs during EPIT is at the cornerstone of the desensitization process.
Identifiants
pubmed: 35779666
pii: S0091-6749(22)00884-3
doi: 10.1016/j.jaci.2022.05.025
pii:
doi:
Substances chimiques
Ovalbumin
9006-59-1
Allergens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1194-1208Informations de copyright
Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.