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Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells.

Bryniarski K, Ptak W, Martin E, Nazimek K, Szczepanik M, Sanak M, Askenase PW - PLoS ONE (2015)

Bottom Line: CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes.We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function.This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.

View Article: PubMed Central - PubMed

Affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Immunology, Jagiellonian University Medical College, Krakow, Poland.

ABSTRACT
Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.

No MeSH data available.


Related in: MedlinePlus

Suppression mediated by dsRNA is not TLR3-dependent and can be blocked by anti-miR to miR-150.a. Treatment of CS-effector cells from either wild type (WT) or TLR3-/- mice with OX Ts Sup of WT mice results in equal suppression of the CS immune response (Group B and D). b. Among different miRNA antagonists (groups C-G), only anti-miR to miR-150 is able to reverse the suppression of CS mediated by TNP Ts Sup QRNA (group C).
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pone.0122991.g004: Suppression mediated by dsRNA is not TLR3-dependent and can be blocked by anti-miR to miR-150.a. Treatment of CS-effector cells from either wild type (WT) or TLR3-/- mice with OX Ts Sup of WT mice results in equal suppression of the CS immune response (Group B and D). b. Among different miRNA antagonists (groups C-G), only anti-miR to miR-150 is able to reverse the suppression of CS mediated by TNP Ts Sup QRNA (group C).

Mentions: To determine if the TLR3 signaling pathway activated by the dsRNA was involved in the suppression mediated by free QRNA, C57BL/6 wild type (WT) and TLR3-/- mice were contact sensitized with OX hapten. Adoptive transfer of CS by harvested CS-effector cells from either WT or TLR3-/- mice was similarly suppressed by Ts Sup from WT mice (Fig 4a, group B and D). Therefore, dsRNA in the PCE or QRNA did not act via TLR3 to suppress the transferred CS-effector cells, although other dsRNA sensing pathways might be involved.


Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells.

Bryniarski K, Ptak W, Martin E, Nazimek K, Szczepanik M, Sanak M, Askenase PW - PLoS ONE (2015)

Suppression mediated by dsRNA is not TLR3-dependent and can be blocked by anti-miR to miR-150.a. Treatment of CS-effector cells from either wild type (WT) or TLR3-/- mice with OX Ts Sup of WT mice results in equal suppression of the CS immune response (Group B and D). b. Among different miRNA antagonists (groups C-G), only anti-miR to miR-150 is able to reverse the suppression of CS mediated by TNP Ts Sup QRNA (group C).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414541&req=5

pone.0122991.g004: Suppression mediated by dsRNA is not TLR3-dependent and can be blocked by anti-miR to miR-150.a. Treatment of CS-effector cells from either wild type (WT) or TLR3-/- mice with OX Ts Sup of WT mice results in equal suppression of the CS immune response (Group B and D). b. Among different miRNA antagonists (groups C-G), only anti-miR to miR-150 is able to reverse the suppression of CS mediated by TNP Ts Sup QRNA (group C).
Mentions: To determine if the TLR3 signaling pathway activated by the dsRNA was involved in the suppression mediated by free QRNA, C57BL/6 wild type (WT) and TLR3-/- mice were contact sensitized with OX hapten. Adoptive transfer of CS by harvested CS-effector cells from either WT or TLR3-/- mice was similarly suppressed by Ts Sup from WT mice (Fig 4a, group B and D). Therefore, dsRNA in the PCE or QRNA did not act via TLR3 to suppress the transferred CS-effector cells, although other dsRNA sensing pathways might be involved.

Bottom Line: CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes.We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function.This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.

View Article: PubMed Central - PubMed

Affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Immunology, Jagiellonian University Medical College, Krakow, Poland.

ABSTRACT
Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.

No MeSH data available.


Related in: MedlinePlus