Dendritic cells and M2 macrophage play an important role in suppression of Th2-mediated inflammation by adipose stem cells-derived extracellular vesicles

Cho, Kyu‐Sup; Kang, Shin Ae; Kim, Sung‐Dong; Mun, Sue-Jean; Yu, Hak Sun; Roh, Hwan‐Jung

doi:10.1016/j.scr.2019.101500

Cited by 37 publications

(33 citation statements)

References 58 publications

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“…As recently evidenced by Cho and colleagues, MSC-EV-based alleviation of Th2 cell-driven immune response against Aspergillus protease antigen was dependent on suppression of antigen-presenting properties of DCs [45]. MSC-Exos induced increased expression of immunosuppressive IL-10 and TGF-β that suppressed maturation of lung DCs [58]. Immature DCs of MSC-Exos-treated mice had reduced expression of co-stimulatory molecules (CD40, CD80 and CD86) and were not capable to optimally activate CD4+Th2 cells, resulting in alleviation of Th2 cell-driven lung inflammation [58].…”

Section: Msc-evs As Next-generation Therapeutics For the Treatment Ofmentioning

confidence: 70%

“…In addition to alveolar macrophages, MSC-EVs may also modulate phenotype and function of lung-infiltrating dendritic cells (DCs) [58]. As recently evidenced by Cho and colleagues, MSC-EV-based alleviation of Th2 cell-driven immune response against Aspergillus protease antigen was dependent on suppression of antigen-presenting properties of DCs [45].…”

Section: Msc-evs As Next-generation Therapeutics For the Treatment Ofmentioning

confidence: 93%

“…MSC-Exos induced increased expression of immunosuppressive IL-10 and TGF-β that suppressed maturation of lung DCs [58]. Immature DCs of MSC-Exos-treated mice had reduced expression of co-stimulatory molecules (CD40, CD80 and CD86) and were not capable to optimally activate CD4+Th2 cells, resulting in alleviation of Th2 cell-driven lung inflammation [58].…”

Section: Msc-evs As Next-generation Therapeutics For the Treatment Ofmentioning

confidence: 99%

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Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Harrell¹,

Jovičić

Djonov

et al. 2019

Cells

482

379

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There is growing evidence that mesenchymal stem cell (MSC)-based immunosuppression was mainly attributed to the effects of MSC-derived extracellular vesicles (MSC-EVs). MSC-EVs are enriched with MSC-sourced bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs), cytokines, chemokines, immunomodulatory factors) that regulate phenotype, function and homing of immune cells. In this review article we emphasized current knowledge regarding molecular mechanisms responsible for the therapeutic effects of MSC-EVs in attenuation of autoimmune and inflammatory diseases. We described the disease-specific cellular targets of MSC-EVs and defined MSC-sourced molecules, which were responsible for MSC-EV-based immunosuppression. Results obtained in a large number of experimental studies revealed that both local and systemic administration of MSC-EVs efficiently suppressed detrimental immune response in inflamed tissues and promoted survival and regeneration of injured parenchymal cells. MSC-EVs-based anti-inflammatory effects were relied on the delivery of immunoregulatory miRNAs and immunomodulatory proteins in inflammatory immune cells (M1 macrophages, dendritic cells (DCs), CD4+Th1 and Th17 cells), enabling their phenotypic conversion into immunosuppressive M2 macrophages, tolerogenic DCs and T regulatory cells. Additionally, through the delivery of mRNAs and miRNAs, MSC-EVs activated autophagy and/or inhibited apoptosis, necrosis and oxidative stress in injured hepatocytes, neurons, retinal cells, lung, gut and renal epithelial cells, promoting their survival and regeneration.

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Section: Msc-evs As Next-generation Therapeutics For the Treatment Ofmentioning

confidence: 70%

Section: Msc-evs As Next-generation Therapeutics For the Treatment Ofmentioning

confidence: 93%

Section: Msc-evs As Next-generation Therapeutics For the Treatment Ofmentioning

confidence: 99%

See 1 more Smart Citation

Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Harrell¹,

Jovičić

Djonov

et al. 2019

Cells

482

379

View full text Add to dashboard Cite

show abstract

“…In a contact hypersensitivity (CHS) mouse model, hUC-MSC-EVs were observed to inhibit CD8+IFN-γ+ cytotoxic T (Tc1) cells and Th1 cell immune responses and to induce Treg expression (45). One underlying mechanism could be that SC-EVs inhibit T cell differentiation into Th1 cells (98) or Th2 cells (52) ( Table 1) while promoting Treg differentiation (91) ( Table 1) by inducing phenotypic transformation of APCs (52,77,91,(97)(98)(99). Another underlying mechanism could be that SC-EVs regulate the expression of the related genes involved in inflammation and immune cell development; for example, they could upregulate miR-let-7b and miR-let-7d and downregulate miR-155 in Treg cells (119).…”

Section: Stem Cell-derived Extracellular Vesicles Inhibit Naive T Celmentioning

confidence: 99%

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Xie

Wang²,

She

et al. 2020

Front. Immunol.

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Recent investigations on the regulatory action of extracellular vesicles (EVs) on immune cells in vitro and in vivo have sparked interest on the subject. As commonly known, EVs are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles containing exosomes, microvesicles, and apoptotic bodies. They are double-layer membrane-bound vesicles enriched with proteins, nucleic acids, and other active compounds. EVs are recognized as a novel apparatus for intercellular communication that acts through delivery of signal molecules. EVs are secreted by almost all cell types, including stem/progenitor cells. The EVs derived from stem/progenitor cells are analogous to the parental cells and inhibit or enhance immune response. This review aims to provide its readers a comprehensive overview of the possible mechanisms underlying the immunomodulatory effects exerted by stem/progenitor cell-derived EVs upon natural killer (NK) cells, dendritic cells (DCs), monocytes/macrophages, microglia, T cells, and B cells.

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“…Images were obtained using a JEM-1011 electron microscope (JEOL, Tokyo, Japan) operated at an acceleration voltage of 100 kV [27,28]. EV markers including CD81 and CD40 were analyzed by western blotting with primary antibodies, anti-CD81 (1 : 1000, Abcam, Cambridge, MA), and anti-CD40 (1 : 1000, Abcam) as previously described [22].…”

Section: Ev Extraction and Characterizationmentioning

confidence: 99%

Screening and Functional Pathway Analysis of Pulmonary Genes Associated with Suppression of Allergic Airway Inflammation by Adipose Stem Cell-Derived Extracellular Vesicles

Kim

Kang

et al. 2020

Stem Cells International

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Background. Although mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have explored the molecular mechanisms of MSC-derived EVs in allergic airway diseases. The objective of this study was to evaluate differentially expressed genes (DEGs) in the lung associated with the suppression of allergic airway inflammation using adipose stem cell- (ASC-) derived EVs. Methods. C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of ASC-derived EVs on allergic airway inflammation, 10 μg/50 μL of EVs were administered intranasally prior to OVA challenge. Lung tissues were removed and DEGs were compared pairwise among the three groups. DEG profiles and hierarchical clustering of the identified genes were analyzed to evaluate changes in gene expression. Real-time PCR was performed to determine the expression levels of genes upregulated after treatment with ASC-derived EVs. Enrichment analysis based on the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to further identify the function of DEGs. Results. Expression of paraoxonase 1 (PON1), brain-expressed X-linked 2 (Bex2), insulin-like growth factor binding protein 6 (Igfbp6), formyl peptide receptor 1 (Fpr1), and secretoglobin family 1C member 1 (Scgb1c1) was significantly increased in asthmatic mice following treatment with ASC-derived EVs. GO enrichment and KEGG pathway analysis showed that these genes were strongly associated with immune system processes and their regulation, cellular processes, single-organism processes, and biological regulation. Conclusion. These results suggest that the DEGs identified in this study (PON1, Bex2, Igfbp6, Fpr1, and Scgb1c1) may be involved in the amelioration of allergic airway inflammation by ASC-derived EVs.

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Dendritic cells and M2 macrophage play an important role in suppression of Th2-mediated inflammation by adipose stem cells-derived extracellular vesicles

Cited by 37 publications

References 58 publications

Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Screening and Functional Pathway Analysis of Pulmonary Genes Associated with Suppression of Allergic Airway Inflammation by Adipose Stem Cell-Derived Extracellular Vesicles

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