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Syngeneic red blood cell-induced extracellular vesicles suppress delayed-type hypersensitivity to self-antigens in mice.
- Source :
-
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2019 Nov; Vol. 49 (11), pp. 1487-1499. Date of Electronic Publication: 2019 Aug 26. - Publication Year :
- 2019
-
Abstract
- Background: At present, the role of autologous cells as antigen carriers inducing immune tolerance is appreciated. Accordingly, intravenous administration of haptenated syngeneic mouse red blood cells (sMRBC) leads to hapten-specific suppression of contact hypersensitivity (CHS) in mice, mediated by light chain-coated extracellular vesicles (EVs). Subsequent studies suggested that mice intravenously administered with sMRBC alone may also generate regulatory EVs, revealing the possible self-tolerogenic potential of autologous erythrocytes.<br />Objectives: The current study investigated the immune effects induced by mere intravenous administration of a high dose of sMRBC in mice.<br />Methods: The self-tolerogenic potential of EVs was determined in a newly developed mouse model of delayed-type hypersensitivity (DTH) to sMRBC. The effects of EV's action on DTH effector cells were evaluated cytometrically. The suppressive activity of EVs, after coating with anti-hapten antibody light chains, was assessed in hapten-induced CHS in wild-type or miRNA-150 <superscript>-/-</superscript> mice.<br />Results: Intravenous administration of sMRBC led to the generation of CD9 + CD81+ EVs that suppressed sMRBC-induced DTH in a miRNA-150-dependent manner. Furthermore, the treatment of DTH effector cells with sMRBC-induced EVs decreased the activation of T cells but enhanced their apoptosis. Finally, EVs coated with antibody light chains inhibited hapten-induced CHS.<br />Conclusions and Clinical Relevance: The current study describes a newly discovered mechanism of self-tolerance induced by the intravenous delivery of a high dose of sMRBC that is mediated by EVs in a miRNA-150-dependent manner. This mechanism implies the concept of naturally occurring immune tolerance, presumably activated by overloading of the organism with altered self-antigens.<br /> (© 2019 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Extracellular Vesicles genetics
Extracellular Vesicles immunology
Immunoglobulin Light Chains genetics
Immunoglobulin Light Chains immunology
Male
Mice
Mice, Knockout
Transplantation, Isogeneic
Autoantigens genetics
Autoantigens immunology
Extracellular Vesicles transplantation
Hypersensitivity genetics
Hypersensitivity immunology
Hypersensitivity pathology
MicroRNAs genetics
MicroRNAs immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2222
- Volume :
- 49
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 31365154
- Full Text :
- https://doi.org/10.1111/cea.13475