Mesenchymal stromal cells ameliorate experimental autoimmune encephalomyelitis by inhibiting CD4 Th17 T cells in a CC chemokine ligand 2-dependent manner. Export

@article{citeulike:4499823, abstract = {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-alpha 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.}, author = {Rafei, M. and Campeau, P. M. and Aguilar-Mahecha, A. and Buchanan, M. and Williams, P. and Birman, E. and Yuan, S. and Young, Y. K. and Boivin, M. N. and Forner, K. and Basik, M. and Galipeau, J.}, citeulike-article-id = {4499823}, citeulike-linkout-0 = {http://dx.doi.org/10.4049/jimmunol.0803962}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19414750}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19414750}, day = {15}, doi = {10.4049/jimmunol.0803962}, issn = {1550-6606}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, keywords = {autoimmune\_diseases, ccl2, chemokine, eae, msc, stem\_cells, t\_cells, th17\_cells}, month = {May}, number = {10}, pages = {5994--6002}, posted-at = {2009-05-10 11:09:14}, priority = {2}, title = {Mesenchymal stromal cells ameliorate experimental autoimmune encephalomyelitis by inhibiting CD4 Th17 T cells in a CC chemokine ligand 2-dependent manner.}, url = {http://dx.doi.org/10.4049/jimmunol.0803962}, volume = {182}, year = {2009} }

TY - JOUR ID - citeulike:4499823 L3 - citeulike-article-id:4499823 N2 - 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-alpha 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. IS - 10 JF - Journal of immunology (Baltimore, Md. : 1950) SN - 1550-6606 EP - 6002 TI - Mesenchymal stromal cells ameliorate experimental autoimmune encephalomyelitis by inhibiting CD4 Th17 T cells in a CC chemokine ligand 2-dependent manner. VL - 182 SP - 5994 KW - autoimmune_diseases KW - ccl2 KW - chemokine KW - eae KW - msc KW - stem_cells KW - t_cells KW - th17_cells AU - Rafei, M AU - Campeau, PM AU - Aguilar-Mahecha, A AU - Buchanan, M AU - Williams, P AU - Birman, E AU - Yuan, S AU - Young, YK AU - Boivin, MN AU - Forner, K AU - Basik, M AU - Galipeau, J PY - 2009/05/15/ UR - http://dx.doi.org/10.4049/jimmunol.0803962 ER -