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Orally Administered Exosomes Suppress Mouse Delayed-Type Hypersensitivity by Delivering miRNA-150 to Antigen-Primed Macrophage APC Targeted by Exosome-Surface Anti-Peptide Antibody Light Chains

1
Department of Immunology, Faculty of Medicine, Medical College, Jagiellonian University, 31-121 Krakow, Poland
2
Section of Rheumatology, Allergy and Immunology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT 06520-8013, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Deceased.
Int. J. Mol. Sci. 2020, 21(15), 5540; https://doi.org/10.3390/ijms21155540
Received: 16 July 2020 / Revised: 29 July 2020 / Accepted: 1 August 2020 / Published: 2 August 2020
(This article belongs to the Special Issue Extracellular Vesicles in Allergy, Autoimmunity and Immune Regulation)
We previously discovered suppressor T cell-derived, antigen (Ag)-specific exosomes inhibiting mouse hapten-induced contact sensitivity effector T cells by targeting antigen-presenting cells (APCs). These suppressive exosomes acted Ag-specifically due to a coating of antibody free light chains (FLC) from Ag-activated B1a cells. Current studies are aimed at determining if similar immune tolerance could be induced in cutaneous delayed-type hypersensitivity (DTH) to the protein Ag (ovalbumin, OVA). Intravenous administration of a high dose of OVA-coupled, syngeneic erythrocytes similarly induced CD3+CD8+ suppressor T cells producing suppressive, miRNA-150-carrying exosomes, also coated with B1a cell-derived, OVA-specific FLC. Simultaneously, OVA-immunized B1a cells produced an exosome subpopulation, originally coated with Ag-specific FLC, that could be rendered suppressive by in vitro association with miRNA-150. Importantly, miRNA-150-carrying exosomes from both suppressor T cells and B1a cells efficiently induced prolonged DTH suppression after single systemic administration into actively immunized mice, with the strongest effect observed after oral treatment. Current studies also showed that OVA-specific FLC on suppressive exosomes bind OVA peptides suggesting that exosome-coating FLC target APCs by binding to peptide-Ag-major histocompatibility complexes. This renders APCs capable of inhibiting DTH effector T cells. Thus, our studies describe a novel immune tolerance mechanism mediated by FLC-coated, Ag-specific, miRNA-150-carrying exosomes that act on the APC and are particularly effective after oral administration. View Full-Text
Keywords: antibody free light chains (FLC); delayed-type hypersensitivity (DTH); extracellular vesicles (EVs); exosomes; miRNA; miRNA-150; oral therapy; suppressor T cells antibody free light chains (FLC); delayed-type hypersensitivity (DTH); extracellular vesicles (EVs); exosomes; miRNA; miRNA-150; oral therapy; suppressor T cells
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MDPI and ACS Style

Nazimek, K.; Bryniarski, K.; Ptak, W.; Groot Kormelink, T.; Askenase, P.W. Orally Administered Exosomes Suppress Mouse Delayed-Type Hypersensitivity by Delivering miRNA-150 to Antigen-Primed Macrophage APC Targeted by Exosome-Surface Anti-Peptide Antibody Light Chains. Int. J. Mol. Sci. 2020, 21, 5540. https://doi.org/10.3390/ijms21155540

AMA Style

Nazimek K, Bryniarski K, Ptak W, Groot Kormelink T, Askenase PW. Orally Administered Exosomes Suppress Mouse Delayed-Type Hypersensitivity by Delivering miRNA-150 to Antigen-Primed Macrophage APC Targeted by Exosome-Surface Anti-Peptide Antibody Light Chains. International Journal of Molecular Sciences. 2020; 21(15):5540. https://doi.org/10.3390/ijms21155540

Chicago/Turabian Style

Nazimek, Katarzyna; Bryniarski, Krzysztof; Ptak, Wlodzimierz; Groot Kormelink, Tom; Askenase, Philip W. 2020. "Orally Administered Exosomes Suppress Mouse Delayed-Type Hypersensitivity by Delivering miRNA-150 to Antigen-Primed Macrophage APC Targeted by Exosome-Surface Anti-Peptide Antibody Light Chains" Int. J. Mol. Sci. 21, no. 15: 5540. https://doi.org/10.3390/ijms21155540

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