Integrin αvβ6 cooperates with resiquimod to restore antigen-specific immune tolerance in airway allergy.
Allergens
/ immunology
Animals
Antigen Presentation
Antigens, Neoplasm
/ genetics
Dendritic Cells
/ immunology
Exosomes
/ immunology
Histocompatibility Antigens Class II
/ metabolism
Imidazoles
/ therapeutic use
Immune Tolerance
Integrins
/ genetics
Membrane Glycoproteins
/ metabolism
Mice
Mice, Inbred BALB C
Mice, Knockout
Nanoparticles
Respiratory Hypersensitivity
/ drug therapy
Signal Transduction
T-Lymphocytes, Regulatory
/ immunology
Toll-Like Receptor 7
/ metabolism
Transforming Growth Factor beta
/ metabolism
Airway allergy
Exosomes
Immunotherapy
Nano-medicine
Therapeutics
Journal
Immunology letters
ISSN: 1879-0542
Titre abrégé: Immunol Lett
Pays: Netherlands
ID NLM: 7910006
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
26
09
2020
revised:
18
12
2020
accepted:
27
12
2020
pubmed:
2
1
2021
medline:
4
1
2022
entrez:
1
1
2021
Statut:
ppublish
Résumé
Integrin αvβ6 can convert the transforming growth factor (TGF)-β precursor to the mature form. Resiquimod (R848) can generate TGF-β-producing regulatory T cells (Treg). Thus, to concurrent administration of specific antigen and R848 may generate antigen-specific Tregs, that is expected to restore immune tolerance in subjects with airway allergic diseases (AAD). A bio-nanoparticle, designated Rexo, containing an antigen/MHC II complex and R848, was naturally assembled in dendritic cells, that was released as an exosome. An AAD mouse model was developed used to test the effects of Rexo on restoring the immune tolerance in the airways. Exposure to R848 failed to induce Tregs in the β6-deficient mouse airway tissues, that were successfully induced in wild type mice. The results were validated inin vitro experiments. R848 activated the TLR7/MyD88/p38 signal pathway to increase the αvβ6 levels in CD4 Rexos can inhibit experimental AAD via inducing antigen-specific Tregs to restore immune tolerance in the airway tissues, suggesting that Rexos have the translational potential to be used in the treatment of AAD.
Sections du résumé
BACKGROUND
Integrin αvβ6 can convert the transforming growth factor (TGF)-β precursor to the mature form. Resiquimod (R848) can generate TGF-β-producing regulatory T cells (Treg). Thus, to concurrent administration of specific antigen and R848 may generate antigen-specific Tregs, that is expected to restore immune tolerance in subjects with airway allergic diseases (AAD).
METHODS
A bio-nanoparticle, designated Rexo, containing an antigen/MHC II complex and R848, was naturally assembled in dendritic cells, that was released as an exosome. An AAD mouse model was developed used to test the effects of Rexo on restoring the immune tolerance in the airways.
RESULTS
Exposure to R848 failed to induce Tregs in the β6-deficient mouse airway tissues, that were successfully induced in wild type mice. The results were validated inin vitro experiments. R848 activated the TLR7/MyD88/p38 signal pathway to increase the αvβ6 levels in CD4
CONCLUSIONS
Rexos can inhibit experimental AAD via inducing antigen-specific Tregs to restore immune tolerance in the airway tissues, suggesting that Rexos have the translational potential to be used in the treatment of AAD.
Identifiants
pubmed: 33385440
pii: S0165-2478(20)30439-9
doi: 10.1016/j.imlet.2020.12.011
pii:
doi:
Substances chimiques
Allergens
0
Antigens, Neoplasm
0
Histocompatibility Antigens Class II
0
Imidazoles
0
Integrins
0
Membrane Glycoproteins
0
Tlr7 protein, mouse
0
Toll-Like Receptor 7
0
Transforming Growth Factor beta
0
integrin alphavbeta6
0
resiquimod
V3DMU7PVXF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
49-58Informations de copyright
Copyright © 2020 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.