IL-4 receptor alpha blockade dampens allergic inflammation and upregulates IL-17A expression to promote Saureus clearance in antigen sensitized mouse skin.
Atopic dermatitis
IL-17A
IL-4Rα
Saureus
type 2 cytokines
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:
10 2023
10 2023
Historique:
received:
09
11
2022
revised:
16
05
2023
accepted:
19
05
2023
pmc-release:
01
10
2024
medline:
9
10
2023
pubmed:
15
6
2023
entrez:
14
6
2023
Statut:
ppublish
Résumé
Skin colonization with Staphylococcus aureus aggravates atopic dermatitis and exaggerates allergic skin inflammation in mice. IL-4 receptor α (IL-4Rα) blockade is beneficial in atopic dermatitis and reduces Saureus skin colonization through unknown mechanisms. The cytokine IL-17A restrains Saureus growth. This study sought to examine the effect of IL-4Rα blockade on Saureus colonization at sites of allergic skin inflammation in mice and determine the mechanism involved. BALB/c mice were epicutaneously sensitized with ovalbumin (OVA). Immediately after, PSVue 794-labeled S aureus strain SF8300 or saline was applied and a single dose of anti-IL-4Rα blocking antibody, a mixture of anti-IL-4Rα and anti-IL-17A blocking antibodies, or IgG isotype controls were administered intradermally. Saureus load was assessed 2 days later by in vivo imaging and enumeration of colony forming units. Skin cellular infiltration was examined by flow cytometry and gene expression by quantitative PCR and transcriptome analysis. IL-4Rα blockade decreased allergic skin inflammation in OVA-sensitized skin, as well as in OVA-sensitized and Saureus-exposed skin, evidenced by significantly decreased epidermal thickening and reduced dermal infiltration by eosinophils and mast cells. This was accompanied by increased cutaneous expression of Il17a and IL-17A-driven antimicrobial genes with no change in Il4 and Il13 expression. IL-4Rα blockade significantly decreased Saureus load in OVA-sensitized and S aureus-exposed skin. IL-17A blockade reversed the beneficial effect of IL-4Rα blockade on Saureus clearance and reduced the cutaneous expression of IL-17A-driven antimicrobial genes. IL-4Rα blockade promotes Saureus clearance from sites of allergic skin inflammation in part by enhancing IL-17A expression.
Sections du résumé
BACKGROUND
Skin colonization with Staphylococcus aureus aggravates atopic dermatitis and exaggerates allergic skin inflammation in mice. IL-4 receptor α (IL-4Rα) blockade is beneficial in atopic dermatitis and reduces Saureus skin colonization through unknown mechanisms. The cytokine IL-17A restrains Saureus growth.
OBJECTIVES
This study sought to examine the effect of IL-4Rα blockade on Saureus colonization at sites of allergic skin inflammation in mice and determine the mechanism involved.
METHODS
BALB/c mice were epicutaneously sensitized with ovalbumin (OVA). Immediately after, PSVue 794-labeled S aureus strain SF8300 or saline was applied and a single dose of anti-IL-4Rα blocking antibody, a mixture of anti-IL-4Rα and anti-IL-17A blocking antibodies, or IgG isotype controls were administered intradermally. Saureus load was assessed 2 days later by in vivo imaging and enumeration of colony forming units. Skin cellular infiltration was examined by flow cytometry and gene expression by quantitative PCR and transcriptome analysis.
RESULTS
IL-4Rα blockade decreased allergic skin inflammation in OVA-sensitized skin, as well as in OVA-sensitized and Saureus-exposed skin, evidenced by significantly decreased epidermal thickening and reduced dermal infiltration by eosinophils and mast cells. This was accompanied by increased cutaneous expression of Il17a and IL-17A-driven antimicrobial genes with no change in Il4 and Il13 expression. IL-4Rα blockade significantly decreased Saureus load in OVA-sensitized and S aureus-exposed skin. IL-17A blockade reversed the beneficial effect of IL-4Rα blockade on Saureus clearance and reduced the cutaneous expression of IL-17A-driven antimicrobial genes.
CONCLUSIONS
IL-4Rα blockade promotes Saureus clearance from sites of allergic skin inflammation in part by enhancing IL-17A expression.
Identifiants
pubmed: 37315811
pii: S0091-6749(23)00755-8
doi: 10.1016/j.jaci.2023.05.025
pmc: PMC10592541
mid: NIHMS1909201
pii:
doi:
Substances chimiques
Interleukin-17
0
Ovalbumin
9006-59-1
Antigens
0
Receptors, Interleukin-4
0
Anti-Infective Agents
0
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
907-915Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007512
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI117673
Pays : United States
Informations de copyright
Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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