The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Inhibiting CD4 Th17 T Cells in a CC Chemokine Ligand 2-Dependent Manner
Open accessAbstract
The administration of ex vivo culture-expanded mesenchymal stromal cells (MSCs) has been shown to reverse symptomatic neuroinflammation observed in experimental autoimmune encephalomyelitis (EAE). The mechanism by which this therapeutic effect occurs remains unknown. In an effort to decipher MSC mode of action, we found that MSC conditioned medium inhibits EAE-derived CD4 T cell activation by suppressing STAT3 phosphorylation via MSC-derived CCL2. Further analysis demonstrates that the effect is dependent on MSC-driven matrix metalloproteinase proteolytic processing of CCL2 to an antagonistic derivative. We also show that antagonistic CCL2 suppresses phosphorylation of AKT and leads to a reciprocal increased phosphorylation of ERK associated with an up-regulation of B7.H1 in CD4 T cells derived from EAE mice. CD4 T cell infiltration of the spinal cord of MSC-treated group was robustly decreased along with reduced plasma levels of IL-17 and TNF-α levels and in vitro from restimulated splenocytes. The key role of MSC-derived CCL2 was confirmed by the observed loss of function of CCL2−/− MSCs in EAE mice. In summary, this is the first report of MSCs modulating EAE biology via the paracrine conversion of CCL2 from agonist to antagonist of CD4 Th17 cell function.
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Cites
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al. (2005) · Nature Immunology · doi:10.1038/ni1261 · Cited by 4,265
Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A., & Sallusto, F. (2007) · Nature Immunology · doi:10.1038/ni1496 · Cited by 1,857 · cited 1×
“Indeed, Th17 CD4 T cells causative of MS/EAE, characterized by a unique CCR4/CCR6 profile (23), are also known to express CCR2 both in humans and mice afflicted with autoimmune diseases (24–26).”
BackgroundIL-17 plays an important role in the development of experimental autoimmune encephalomyelitis
Komiyama, Y., Nakae, S., Matsuki, T., Nambu, A., Ishigame, H., Kakuta, S., Sudo, K., & Iwakura, Y. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.1.566 · Cited by 1,536
Multiple sclerosis: a complicated picture of autoimmunity
McFarland, H. F., & Martin, R. (2007) · Nature Immunology · doi:10.1038/ni1507 · Cited by 985
Kim, Y. J., Kim, H. K., Cho, H. H., Bae, Y. C., Suh, K. T., & Jung, J. S. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000110447 · Cited by 298
Cited by
Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)
Constantinescu, C. S., Farooqi, N., O'Brien, K., & Gran, B. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01302.x · Cited by 1,523
Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications
Wang, Y., Chen, X., Cao, W., & Shi, Y. (2014) · Nature Immunology · doi:10.1038/ni.3002 · Cited by 1,452
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
Multipotent mesenchymal stromal cells and the innate immune system
Le Blanc, K., & Mougiakakos, D. (2012) · Nature Reviews Immunology · doi:10.1038/nri3209 · Cited by 1,018
Metadata
- Authors
- Rafei, M., Campeau, P. M., Aguilar-Mahecha, A., Buchanan, M., Williams, P., Birman, E., Yuan, S., Young, Y. K., Boivin, M.-N., Forner, K., Basik, M., & Galipeau, J.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-05
- Volume
- 182
- Issue
- 10
- Pages
- 5994-6002
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2103893610
- Cited by
- 381
- References
- 7
- FWCI
- 16.06
- Type
- journal article
- Language
- en
- Open access
- bronze
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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.
