The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Mesenchymal Stem Cells Inhibit the Differentiation of Dendritic Cells Through an Interleukin-6-Dependent Mechanism
Abstract
Mesenchymal stem cells (MSC) are of particular interest for their potential clinical use in tissue engineering as well as for their capacity to reduce the incidence and severity of graft-versus-host disease in allogeneic transplantation. We have previously shown that MSC-mediated immune suppression acts via the secretion of soluble factor(s) induced upon stimulation. The aim of this study was to identify the molecule(s) involved and the underlying mechanism(s). We show that murine MSC secrete high levels of interleukin (IL)-6 and vascular endothelial growth factor, which are directly correlated to the inhibition of T-cell proliferation. The T-cell activation is partially restored upon addition of a neutralizing anti-IL-6 antibody or the prostaglandin E2 inhibitor indomethacin. Interestingly, no indoleamine 2,3-dioxygenase activity was detected in our conditions. Instead, we show that MSC reduce the expression of major histocompatibility complex class II, CD40, and CD86 costimulatory molecules on mature dendritic cells (DC), which was responsible for a decrease in T-cell proliferation. Moreover, we show that the differentiation of bone marrow progenitors into DC cultured with conditioned supernatants from MSC was partly inhibited through the secretion of IL-6. Altogether, these data suggest that IL-6 is involved in the immunoregulatory mechanism mediated by MSC through a partial inhibition of DC differentiation but is probably not the main mechanism. Disclosure of potential conflicts of interest is found at the end of this article.
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Cites
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Cited by
Mesenchymal stem cell perspective: cell biology to clinical progress
Pittenger, M. F., Discher, D. E., Péault, B. M., Phinney, D. G., Hare, J. M., & Caplan, A. I. (2019) · npj Regenerative Medicine · doi:10.1038/s41536-019-0083-6 · Cited by 2,008
Mesenchymal stem cells and immunomodulation: current status and future prospects
Gao, F., Chiu, S. M., Motan, D. A. L., Zhang, Z., Chen, L., Ji, H.-L., Tse, H.-F., Fu, Q.-L., & Lian, Q. (2016) · Cell Death & Disease · doi:10.1038/cddis.2015.327 · Cited by 1,121
Stem Cell Paracrine Actions and Tissue Regeneration
Baraniak, P. R., & McDevitt, T. C. (2010) · Regenerative Medicine · doi:10.2217/rme.09.74 · Cited by 843
Immunobiology of mesenchymal stem cells
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Han, Y., Yang, J., Fang, J., Zhou, Y., Candi, E., Wang, J., Hua, D., Shao, C., & Shi, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00932-0 · Cited by 720
Metadata
- Authors
- Djouad, F., Charbonnier, L.-M., Bouffi, C., Louis-Plence, P., Bony, C., Apparailly, F., Cantos, C., Jorgensen, C., & Noël, D.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-05-17
- Volume
- 25
- Issue
- 8
- Pages
- 2025-2032
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2025294489
- Cited by
- 667
- References
- 27
- FWCI
- 11.71
- Type
- journal article
- Language
- en
- Open access
- closed
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- Djouad, F., Charbonnier, L.-M., Bouffi, C., Louis-Plence, P., Bony, C., Apparailly, F., Cantos, C., Jorgensen, C., & Noël, D. (2007). Mesenchymal Stem Cells Inhibit the Differentiation of Dendritic Cells Through an Interleukin-6-Dependent Mechanism. Stem Cells. https://doi.org/10.1634/stemcells.2006-0548
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