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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052
Cluster analysis and display of genome-wide expression patterns
Eisen, M. B., Spellman, P. T., Brown, P. O., & Botstein, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14863 · Cited by 16,184
Caplan, A. I. (1991) · Journal of Orthopaedic Research · doi:10.1002/jor.1100090504 · Cited by 6,548
Human mesenchymal stem cells modulate allogeneic immune cell responses
Aggarwal, S., & Pittenger, M. F. (2005) · Blood · doi:10.1182/blood-2004-04-1559 · Cited by 4,511
Di Nicola, M., Carlo-Stella, C., Magni, M., Milanesi, M., Longoni, P. D., Matteucci, P., Grisanti, S., & Gianni, A. M. (2002) · Blood · doi:10.1182/blood.v99.10.3838 · Cited by 3,226
Le Blanc, K., Rasmusson, I., Sundberg, B., Götherström, C., Hassan, M., Uzunel, M., & Ringdén, O. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16104-7 · Cited by 2,734
Ido expression by dendritic cells: tolerance and tryptophan catabolism
Mellor, A. L., & Munn, D. H. (2004) · Nature Reviews Immunology · doi:10.1038/nri1457 · Cited by 2,341
Horwitz, E. M., Prockop, D. J., Fitzpatrick, L. A., Koo, W. W. K., Gordon, P. L., Neel, M., Sussman, M., Orchard, P., Marx, J. C., Pyeritz, R. E., et al. (1999) · Nature Medicine · doi:10.1038/6529 · Cited by 1,824
Mesenchymal stem cells: clinical applications and biological characterization
Barry, F. P., & Murphy, J. M. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2003.11.001 · Cited by 1,665
Meisel, R., Zibert, A., Laryea, M., Göbel, U., Däubener, W., & Dilloo, D. (2004) · Blood · doi:10.1182/blood-2003-11-3909 · Cited by 1,646
Tse, W. T., Pendleton, J. D., Beyer, W. M., Egalka, M. C., & Guinan, E. C. (2003) · Transplantation · doi:10.1097/01.tp.0000045055.63901.a9 · Cited by 1,500
Jiang, X.-X., Zhang, Y., Liu, B., Zhang, S.-X., Wu, Y., Yu, X.-D., & Mao, N. (2005) · Blood · doi:10.1182/blood-2004-02-0586 · Cited by 1,346
Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals
Djouad, F., Plence, P., Bony, C., Tropel, P., Apparailly, F., Sany, J., Noël, D., & Jorgensen, C. (2003) · Blood · doi:10.1182/blood-2003-04-1193 · Cited by 1,166
Self-citationBone marrow mesenchymal stem cells induce division arrest anergy of activated T cells
Glennie, S., Soeiro, I., Dyson, P. J., Lam, E. W.-F., & Dazzi, F. (2005) · Blood · doi:10.1182/blood-2004-09-3696 · Cited by 1,150
Beyth, S., Borovsky, Z., Mevorach, D., Liebergall, M., Gazit, Z., Aslan, H., Galun, E., & Rachmilewitz, J. (2005) · Blood · doi:10.1182/blood-2004-07-2921 · Cited by 1,034
IL-6 switches the differentiation of monocytes from dendritic cells to macrophages
Chomarat, P., Banchereau, J., Davoust, J., & Karolina Palucka, A. (2000) · Nature Immunology · doi:10.1038/82763 · Cited by 906
Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes
Naik, S. H., Metcalf, D., van Nieuwenhuijze, A., Wicks, I., Wu, L., O'Keeffe, M., & Shortman, K. (2006) · Nature Immunology · doi:10.1038/ni1340 · Cited by 605
VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression
Ohm, J. E., Gabrilovich, D. I., Sempowski, G. D., Kisseleva, E., Parman, K. S., Nadaf, S., & Carbone, D. P. (2003) · Blood · doi:10.1182/blood-2002-07-1956 · Cited by 538
Biologic effects of anti-interleukin-6 murine monoclonal antibody in advanced multiple myeloma
Bataille, R., Barlogie, B., Lu, Z., Rossi, J., Lavabre-Bertrand, T., Beck, T., Wijdenes, J., Brochier, J., & Klein, B. (1995) · Blood · doi:10.1182/blood.v86.2.685.bloodjournal862685 · Cited by 269
Engineered allogeneic mesenchymal stem cells repair femoral segmental defect in rats
Tsuchida, H., Hashimoto, J., Crawford, E., Manske, P., & Lou, J. (2003) · Journal of Orthopaedic Research · doi:10.1016/s0736-0266(02)00108-0 · Cited by 194
Hegde, S., Pahne, J., & Smola, S. (2004) · The FASEB Journal · doi:10.1096/fj.03-0969fje · Cited by 152
Inoue, H., Takamori, M., Shimoyama, Y., Ishibashi, H., Yamamoto, S., & Koshihara, Y. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704705 · Cited by 139
Transplanted bone marrow cells localize to fracture callus in a mouse model
Devine, M. J., Mierisch, C., Jang, E., Anderson, P., & Balian, G. (2002) · Journal of Orthopaedic Research® · doi:10.1016/s0736-0266(02)00051-7 · Cited by 122
Molecular characterization of allospecific T suppressor and tolerogenic dendritic cells: review
Suciu‐Foca, N., Manavalan, J. S., Scotto, L., Kim‐Schulze, S., Galluzzo, S., Naiyer, A. J., Fan, J., Vlad, G., & Cortesini, R. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2004.09.003 · Cited by 102
Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells
Mitani, H., Katayama, N., Araki, H., Ohishi, K., Kobayashi, K., Suzuki, H., Nishii, K., Masuya, M., Yasukawa, K., Minami, N., et al. (2000) · British Journal of Haematology · doi:10.1046/j.1365-2141.2000.02020.x · Cited by 99
Non-antigen specific CD8+ T suppressor lymphocytes
Filaci, G., Fravega, M., Fenoglio, D., Rizzi, M., Negrini, S. M., Viggiani, R., & Indiveri, F. (2004) · Clinical and Experimental Medicine · doi:10.1007/s10238-004-0042-3 · Cited by 56
Interleukin-1 Inhibits Gamma Interferon-Induced Bacteriostasis in Human Uroepithelial Cells
Däubener, W., Hucke, C., Seidel, K., Hadding, U., & Mackenzie, C. (1999) · Infection and Immunity · doi:10.1128/iai.67.11.5615-5620.1999 · Cited by 30
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
Ma, S., Xie, N., Li, W., Yuan, B., Shi, Y., & Wang, Y. (2014) · Cell Death & Differentiation · doi:10.1038/cdd.2013.158 · Cited by 771
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
