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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.
- Source :
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International journal of molecular sciences [Int J Mol Sci] 2020 Aug 02; Vol. 21 (15). Date of Electronic Publication: 2020 Aug 02. - Publication Year :
- 2020
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Abstract
- 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 <superscript>+</superscript> CD8 <superscript>+</superscript> 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.
- Subjects :
- Animals
Antigens immunology
Female
Immune Tolerance immunology
Immunoglobulin Light Chains immunology
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Knockout
MicroRNAs genetics
Ovalbumin immunology
T-Lymphocytes immunology
T-Lymphocytes metabolism
Antibodies immunology
Antigen-Presenting Cells immunology
Exosomes immunology
Hypersensitivity, Delayed immunology
Macrophages immunology
MicroRNAs immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32748889
- Full Text :
- https://doi.org/10.3390/ijms21155540