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Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
Enhanced generation of reactive oxygen intermediates by suppressor T cell-derived exosome-treated macrophages
Katarzyna Nazimek, Bernadeta Nowak, Janusz Marcinkiewicz
1Department of Immunology, Jagiellonian University Medical College, Krakow, Poland. krzysztof.bryniarski@uj.edu.pl.
Abstract:
Macrophages (Mφ) as efficient phagocytes able to present the antigen and playing an effector role induce and orchestrate the immune response also through the release of soluble factors. Recently described T CD8+ cell-derived suppressive exosomes carrying miRNA-150, that act antigen-specifically, seem to inhibit murine contact sensitivity reaction indirectly by affecting antigen presenting cells, especially Mφ. Present studies investigated the influence of suppressive exosomes on secretory activity of Mφ assessed as their ability to generate reactive oxygen intermediates (ROIs), nitric oxide, cytokines as well as their viability and expression of antigen phagocytosis and presentation markers. Interestingly, in vivo and in vitro treatment of Mφ with assayed hapten-specific exosomes affected only ROIs generation, significantly enhancing their production. Current results suggest that ROIs may participate in antigen-specific tolerance mechanism mediated by suppressive T lymphocyte-derived exosome-influenced Mφ, by inhibition of effector T cell proliferation and induction of T regulatory lymphocytes.
Insights
Suppressor T cell exosomes carrying miRNA-150 enhance reactive oxygen intermediates (ROIs) production in macrophages (Mφ). This suggests ROIs may mediate antigen-specific tolerance by influencing Mφ activity and T cell responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages (Mφ) are key antigen-presenting cells orchestrating immune responses.
- T CD8+ cell-derived exosomes containing miRNA-150 can suppress immune reactions by affecting Mφ.
- The precise impact of these exosomes on Mφ secretory activity requires further investigation.
Purpose of the Study:
- To investigate the influence of suppressive exosomes on macrophage secretory activity.
- To assess the effects on reactive oxygen intermediates (ROIs), nitric oxide, cytokines, viability, and antigen presentation markers.
Main Methods:
- In vivo and in vitro treatment of Mφ with hapten-specific exosomes.
- Assessment of Mφ secretory functions, including ROI generation.
- Evaluation of Mφ viability and expression of antigen presentation markers.
Main Results:
- Exosome treatment significantly enhanced ROI generation in Mφ.
- No significant effects were observed on nitric oxide, cytokine release, viability, or antigen presentation markers.
- Hapten-specific exosomes modulated Mφ activity.
Conclusions:
- Enhanced ROI production by Mφ may play a role in antigen-specific tolerance.
- Suppressor T cell-derived exosomes influence Mφ to potentially inhibit effector T cell proliferation and induce regulatory T cells.
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