Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton
Mesenchymal stromal cells (MSCs) are adult, multipotent cells of mesodermal origin representing the progenitors of all stromal tissues. MSCs possess significant and broad immunomodulatory functions affecting both adaptive and innate immune responses once MSCs are primed by the inflammatory microenvi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00446/full |
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| author | Annalisa Adamo Jessica Brandi Simone Caligola Pietro Delfino Riccardo Bazzoni Roberta Carusone Daniela Cecconi Rosalba Giugno Marcello Manfredi Marcello Manfredi Elisa Robotti Emilio Marengo Emilio Marengo Giulio Bassi Paul Takam Kamga Giada Dal Collo Alessandro Gatti Angela Mercuri Maddalena Arigoni Martina Olivero Raffaele A. Calogero Mauro Krampera |
| author_facet | Annalisa Adamo Jessica Brandi Simone Caligola Pietro Delfino Riccardo Bazzoni Roberta Carusone Daniela Cecconi Rosalba Giugno Marcello Manfredi Marcello Manfredi Elisa Robotti Emilio Marengo Emilio Marengo Giulio Bassi Paul Takam Kamga Giada Dal Collo Alessandro Gatti Angela Mercuri Maddalena Arigoni Martina Olivero Raffaele A. Calogero Mauro Krampera |
| author_sort | Annalisa Adamo |
| collection | DOAJ |
| description | Mesenchymal stromal cells (MSCs) are adult, multipotent cells of mesodermal origin representing the progenitors of all stromal tissues. MSCs possess significant and broad immunomodulatory functions affecting both adaptive and innate immune responses once MSCs are primed by the inflammatory microenvironment. Recently, the role of extracellular vesicles (EVs) in mediating the therapeutic effects of MSCs has been recognized. Nevertheless, the molecular mechanisms responsible for the immunomodulatory properties of MSC-derived EVs (MSC-EVs) are still poorly characterized. Therefore, we carried out a molecular characterization of MSC-EV content by high-throughput approaches. We analyzed miRNA and protein expression profile in cellular and vesicular compartments both in normal and inflammatory conditions. We found several proteins and miRNAs involved in immunological processes, such as MOES, LG3BP, PTX3, and S10A6 proteins, miR-155-5p, and miR-497-5p. Different in silico approaches were also performed to correlate miRNA and protein expression profile and then to evaluate the putative molecules or pathways involved in immunoregulatory properties mediated by MSC-EVs. PI3K-AKT signaling pathway and the regulation of actin cytoskeleton were identified and functionally validated in vitro as key mediators of MSC/B cell communication mediated by MSC-EVs. In conclusion, we identified different molecules and pathways responsible for immunoregulatory properties mediated by MSC-EVs, thus identifying novel therapeutic targets as safer and more useful alternatives to cell or EV-based therapeutic approaches. |
| first_indexed | 2024-04-13T01:16:24Z |
| format | Article |
| id | doaj.art-30e1404bd270430c963c2de9b26650d0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T01:16:24Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-30e1404bd270430c963c2de9b26650d02022-12-22T03:08:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00446432255Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin CytoskeletonAnnalisa Adamo0Jessica Brandi1Simone Caligola2Pietro Delfino3Riccardo Bazzoni4Roberta Carusone5Daniela Cecconi6Rosalba Giugno7Marcello Manfredi8Marcello Manfredi9Elisa Robotti10Emilio Marengo11Emilio Marengo12Giulio Bassi13Paul Takam Kamga14Giada Dal Collo15Alessandro Gatti16Angela Mercuri17Maddalena Arigoni18Martina Olivero19Raffaele A. Calogero20Mauro Krampera21Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, ItalyProteomics and Mass Spectrometry Laboratory, Department of Biotechnology, University of Verona, Verona, ItalyDepartment of Computer Science, University of Verona, Verona, ItalyDepartment of Biotechnology, University of Verona, Verona, ItalyStem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, ItalyStem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, ItalyProteomics and Mass Spectrometry Laboratory, Department of Biotechnology, University of Verona, Verona, ItalyDepartment of Computer Science, University of Verona, Verona, ItalyDepartment of Sciences and Technological Innovation, University of Piemonte Orientale, Alessandria, ItalyCenter for Translational Research on Autoimmune and Allergic Diseases (CAAD), Novara, ItalyDepartment of Sciences and Technological Innovation, University of Piemonte Orientale, Alessandria, ItalyDepartment of Sciences and Technological Innovation, University of Piemonte Orientale, Alessandria, ItalyCenter for Translational Research on Autoimmune and Allergic Diseases (CAAD), Novara, ItalyStem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, ItalyStem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, ItalyStem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, ItalyStem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, ItalyStem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Turin, ItalyDepartment of Oncology, University of Torino, Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Turin, ItalyStem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, ItalyMesenchymal stromal cells (MSCs) are adult, multipotent cells of mesodermal origin representing the progenitors of all stromal tissues. MSCs possess significant and broad immunomodulatory functions affecting both adaptive and innate immune responses once MSCs are primed by the inflammatory microenvironment. Recently, the role of extracellular vesicles (EVs) in mediating the therapeutic effects of MSCs has been recognized. Nevertheless, the molecular mechanisms responsible for the immunomodulatory properties of MSC-derived EVs (MSC-EVs) are still poorly characterized. Therefore, we carried out a molecular characterization of MSC-EV content by high-throughput approaches. We analyzed miRNA and protein expression profile in cellular and vesicular compartments both in normal and inflammatory conditions. We found several proteins and miRNAs involved in immunological processes, such as MOES, LG3BP, PTX3, and S10A6 proteins, miR-155-5p, and miR-497-5p. Different in silico approaches were also performed to correlate miRNA and protein expression profile and then to evaluate the putative molecules or pathways involved in immunoregulatory properties mediated by MSC-EVs. PI3K-AKT signaling pathway and the regulation of actin cytoskeleton were identified and functionally validated in vitro as key mediators of MSC/B cell communication mediated by MSC-EVs. In conclusion, we identified different molecules and pathways responsible for immunoregulatory properties mediated by MSC-EVs, thus identifying novel therapeutic targets as safer and more useful alternatives to cell or EV-based therapeutic approaches.https://www.frontiersin.org/article/10.3389/fimmu.2019.00446/fullextracellular vesiclesmesenchymal stromal cellsB cellshigh-throughput analysisPI3K-AKT signaling pathwayactin cytoskeleton |
| spellingShingle | Annalisa Adamo Jessica Brandi Simone Caligola Pietro Delfino Riccardo Bazzoni Roberta Carusone Daniela Cecconi Rosalba Giugno Marcello Manfredi Marcello Manfredi Elisa Robotti Emilio Marengo Emilio Marengo Giulio Bassi Paul Takam Kamga Giada Dal Collo Alessandro Gatti Angela Mercuri Maddalena Arigoni Martina Olivero Raffaele A. Calogero Mauro Krampera Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton Frontiers in Immunology extracellular vesicles mesenchymal stromal cells B cells high-throughput analysis PI3K-AKT signaling pathway actin cytoskeleton |
| title | Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton |
| title_full | Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton |
| title_fullStr | Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton |
| title_full_unstemmed | Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton |
| title_short | Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton |
| title_sort | extracellular vesicles mediate mesenchymal stromal cell dependent regulation of b cell pi3k akt signaling pathway and actin cytoskeleton |
| topic | extracellular vesicles mesenchymal stromal cells B cells high-throughput analysis PI3K-AKT signaling pathway actin cytoskeleton |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00446/full |
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