The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells
Abstract
The molecular mechanisms by which mesenchymal stem cells (MSCs) suppress T-cell proliferation are poorly understood, and whether a soluble factor plays a major role remains controversial. Here we demonstrate that the T-cell–receptor complex is not a target for the suppression, suggesting that downstream signals mediate the suppression. We found that Stat5 phosphorylation in T cells is suppressed in the presence of MSCs and that nitric oxide (NO) is involved in the suppression of Stat5 phosphorylation and T-cell proliferation. The induction of inducible NO synthase (NOS) was readily detected in MSCs but not T cells, and a specific inhibitor of NOS reversed the suppression of Stat5 phosphorylation and T-cell proliferation. This production of NO in the presence of MSCs was mediated by CD4 or CD8 T cells but not by CD19 B cells. Furthermore, inhibitors of prostaglandin synthase or NOS restored the proliferation of T cells, whereas an inhibitor of indoleamine 2,3-dioxygenase and a transforming growth factor–β–neutralizing antibody had no effect. Finally, MSCs from inducible NOS−/− mice had a reduced ability to suppress T-cell proliferation. Taken together, these results suggest that NO produced by MSCs is one of the major mediators of T-cell suppression by MSCs.
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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
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
Nitric oxide and the immune response
Bogdan, C. (2001) · Nature Immunology · doi:10.1038/ni1001-907 · Cited by 3,447
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
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Krampera, M., Glennie, S., Dyson, J., Scott, D., Laylor, R., Simpson, E., & Dazzi, F. (2003) · Blood · doi:10.1182/blood-2002-07-2104 · Cited by 1,598
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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
Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells
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Cited by
Ren, G., Zhang, L., Zhao, X., Xu, G., Zhang, Y., Roberts, A. I., Zhao, R. C., & Shi, Y. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2007.11.014 · Cited by 2,101
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
Mechanisms involved in the therapeutic properties of mesenchymal stem cells
da Silva Meirelles, L., Fontes, A. M., Covas, D. T., & Caplan, A. I. (2009) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2009.10.002 · Cited by 1,436
Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases
Shi, Y., Wang, Y., Li, Q., Liu, K., Hou, J., Shao, C., & Wang, Y. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0023-5 · Cited by 1,223
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
Metadata
- Authors
- Sato, K., Ozaki, K., Oh, I., Meguro, A., Hatanaka, K., Nagai, T., Muroi, K., & Ozawa, K.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-09-19
- Volume
- 109
- Issue
- 1
- Pages
- 228-234
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2051297632
- Cited by
- 954
- References
- 33
- FWCI
- 15.30
- Type
- journal article
- Language
- en
- Open access
- closed
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- Sato, K., Ozaki, K., Oh, I., Meguro, A., Hatanaka, K., Nagai, T., Muroi, K., & Ozawa, K. (2007). Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood. https://doi.org/10.1182/blood-2006-02-002246
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