Syngeneic red blood cell-induced extracellular vesicles suppress delayed-type hypersensitivity to self-antigens in mice. 2019

Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
Department of Immunology, Jagiellonian University Medical College, Krakow, Poland.

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. The current study investigated the immune effects induced by mere intravenous administration of a high dose of sMRBC in mice. 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-/- mice. 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. 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.

UI MeSH Term Description Entries
D006967 Hypersensitivity Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. Allergy,Allergic Reaction,Allergic Reactions,Allergies,Hypersensitivities,Reaction, Allergic,Reactions, Allergic
D007147 Immunoglobulin Light Chains Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule. Ig Light Chains,Immunoglobulins, Light-Chain,Immunoglobulin Light Chain,Immunoglobulin Light-Chain,Light-Chain Immunoglobulins,Chains, Ig Light,Chains, Immunoglobulin Light,Immunoglobulins, Light Chain,Light Chain Immunoglobulins,Light Chain, Immunoglobulin,Light Chains, Ig,Light Chains, Immunoglobulin,Light-Chain, Immunoglobulin
D008297 Male Males
D000067128 Extracellular Vesicles Membrane limited structures derived from cell membranes and cytoplasmic material, and released into EXTRACELLULAR SPACE. They circulate through the EXTRACELLULAR FLUID and through the peripheral blood in the MICROVASCULATURE where cells, much larger, cannot, thereby affecting a variety of intercellular communication processes. Apoptotic Bodies,Exovesicles,Apoptotic Body,Bodies, Apoptotic,Body, Apoptotic,Exovesicle,Extracellular Vesicle,Vesicle, Extracellular,Vesicles, Extracellular
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001324 Autoantigens Endogenous tissue constituents with the ability to interact with AUTOANTIBODIES and cause an immune response. Autoantigen,Autologous Antigen,Autologous Antigens,Self-Antigen,Self-Antigens,Antigen, Autologous,Antigens, Autologous,Self Antigen,Self Antigens
D014185 Transplantation, Isogeneic Transplantation between genetically identical individuals, i.e., members of the same species with identical histocompatibility antigens, such as monozygotic twins, members of the same inbred strain, or members of a hybrid population produced by crossing certain inbred strains. Transplantation, Syngeneic,Isogeneic Transplantation,Isograft Transplantation,Isografting,Syngeneic Transplantation,Transplantation, Isograft
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out
D035683 MicroRNAs Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing. RNA, Small Temporal,Small Temporal RNA,miRNA,stRNA,Micro RNA,MicroRNA,Primary MicroRNA,Primary miRNA,miRNAs,pre-miRNA,pri-miRNA,MicroRNA, Primary,RNA, Micro,Temporal RNA, Small,miRNA, Primary,pre miRNA,pri miRNA

Related Publications

Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
January 1987, Neoplasma,
Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
February 1985, Immunobiology,
Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
November 1982, European journal of immunology,
Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
February 1984, Scandinavian journal of immunology,
Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
November 1986, Arerugi = [Allergy],
Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
November 1984, Scandinavian journal of immunology,
Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
November 1989, Transplantation,
Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
April 1988, Scandinavian journal of immunology,
Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
October 1986, Journal of immunology (Baltimore, Md. : 1950),
Katarzyna Nazimek, and Eugenio Bustos-Morán, and Noelia Blas-Rus, and Bernadeta Nowak, and Włodzimierz Ptak, and Philip W Askenase, and Francisco Sánchez-Madrid, and Krzysztof Bryniarski
May 1984, Clinical and experimental immunology,
Copied contents to your clipboard!