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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Autores principales:	Akaitz Dorronsoro, Valérie Lang, Izaskun Ferrin, Jon Fernández-Rueda, Lorea Zabaleta, Estibaliz Pérez-Ruiz, Pilar Sepúlveda, César Trigueros
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/677c874354c94bd3925f46d7ec631002
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spelling	oai:doaj.org-article:677c874354c94bd3925f46d7ec6310022021-12-02T12:42:18ZIntracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation10.1038/s41598-020-78864-42045-2322https://doaj.org/article/677c874354c94bd3925f46d7ec6310022020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78864-4https://doaj.org/toc/2045-2322Abstract 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.Akaitz DorronsoroValérie LangIzaskun FerrinJon Fernández-RuedaLorea ZabaletaEstibaliz Pérez-RuizPilar SepúlvedaCésar TriguerosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	intracellular role of il-6 in mesenchymal stromal cell immunosuppression and proliferation
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/677c874354c94bd3925f46d7ec631002
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Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation

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