Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation
Abstract Interleukin (IL)-6 is a pleiotropic cytokine involved in the regulation of hematological and immune responses. IL-6 is secreted chiefly by stromal cells, but little is known about its precise role in the homeostasis of human mesenchymal stromal cells (hMSCs) and the role it may play in hMSC...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2020-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-78864-4 |
| _version_ | 1830082829715767296 |
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| author | Akaitz Dorronsoro Valérie Lang Izaskun Ferrin Jon Fernández-Rueda Lorea Zabaleta Estibaliz Pérez-Ruiz Pilar Sepúlveda César Trigueros |
| author_facet | Akaitz Dorronsoro Valérie Lang Izaskun Ferrin Jon Fernández-Rueda Lorea Zabaleta Estibaliz Pérez-Ruiz Pilar Sepúlveda César Trigueros |
| author_sort | Akaitz Dorronsoro |
| collection | DOAJ |
| description | Abstract Interleukin (IL)-6 is a pleiotropic cytokine involved in the regulation of hematological and immune responses. IL-6 is secreted chiefly by stromal cells, but little is known about its precise role in the homeostasis of human mesenchymal stromal cells (hMSCs) and the role it may play in hMSC-mediated immunoregulation. We studied the role of IL-6 in the biology of bone marrow derived hMSC in vitro by silencing its expression using short hairpin RNA targeting. Our results show that IL-6 is involved in immunosuppression triggered by hMSCs. Cells silenced for IL-6 showed a reduced capacity to suppress activated T-cell proliferation. Moreover, silencing of IL-6 significantly blocked the capacity of hMSCs to proliferate. Notably, increasing the intracellular level of IL-6 but not recovering the extracellular level could restore the proliferative impairment observed in IL-6-silenced hMSC. Our data indicate that IL-6 signals in hMSCs by a previously undescribed intracellular mechanism. |
| first_indexed | 2024-12-14T16:10:26Z |
| format | Article |
| id | doaj.art-677c874354c94bd3925f46d7ec631002 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T16:10:26Z |
| publishDate | 2020-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-677c874354c94bd3925f46d7ec6310022022-12-21T22:55:01ZengNature PortfolioScientific Reports2045-23222020-12-0110111210.1038/s41598-020-78864-4Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferationAkaitz Dorronsoro0Valérie Lang1Izaskun Ferrin2Jon Fernández-Rueda3Lorea Zabaleta4Estibaliz Pérez-Ruiz5Pilar Sepúlveda6César Trigueros7Mesenchymal Stem Cell Laboratory, Fundación Inbiomed, Foundation for Stem Cell ResearchMesenchymal Stem Cell Laboratory, Fundación Inbiomed, Foundation for Stem Cell ResearchMesenchymal Stem Cell Laboratory, Fundación Inbiomed, Foundation for Stem Cell ResearchMesenchymal Stem Cell Laboratory, Fundación Inbiomed, Foundation for Stem Cell ResearchMesenchymal Stem Cell Laboratory, Fundación Inbiomed, Foundation for Stem Cell ResearchMesenchymal Stem Cell Laboratory, Fundación Inbiomed, Foundation for Stem Cell ResearchRegenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La FeMesenchymal Stem Cell Laboratory, Fundación Inbiomed, Foundation for Stem Cell ResearchAbstract Interleukin (IL)-6 is a pleiotropic cytokine involved in the regulation of hematological and immune responses. IL-6 is secreted chiefly by stromal cells, but little is known about its precise role in the homeostasis of human mesenchymal stromal cells (hMSCs) and the role it may play in hMSC-mediated immunoregulation. We studied the role of IL-6 in the biology of bone marrow derived hMSC in vitro by silencing its expression using short hairpin RNA targeting. Our results show that IL-6 is involved in immunosuppression triggered by hMSCs. Cells silenced for IL-6 showed a reduced capacity to suppress activated T-cell proliferation. Moreover, silencing of IL-6 significantly blocked the capacity of hMSCs to proliferate. Notably, increasing the intracellular level of IL-6 but not recovering the extracellular level could restore the proliferative impairment observed in IL-6-silenced hMSC. Our data indicate that IL-6 signals in hMSCs by a previously undescribed intracellular mechanism.https://doi.org/10.1038/s41598-020-78864-4 |
| spellingShingle | Akaitz Dorronsoro Valérie Lang Izaskun Ferrin Jon Fernández-Rueda Lorea Zabaleta Estibaliz Pérez-Ruiz Pilar Sepúlveda César Trigueros Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation Scientific Reports |
| title | Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation |
| title_full | Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation |
| title_fullStr | Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation |
| title_full_unstemmed | Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation |
| title_short | Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation |
| title_sort | intracellular role of il 6 in mesenchymal stromal cell immunosuppression and proliferation |
| url | https://doi.org/10.1038/s41598-020-78864-4 |
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