Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation

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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.

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Dorronsoro, A., Lang, V., Ferrin, I., Fernández-Rueda, J., Zabaleta, L., Pérez-Ruiz, E., … Trigueros, C. (2020). Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-78864-4

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