- Title
- Potently immunosuppressive 5-fluorouracil-resistant mesenchymal stromal cells completely remit an experimental autoimmune disease
- Creator
- Oh, Ding; Cui, Peng; Hosseini, Hamid; Mosse, Jennifer; Toh, Ban-Hock; Chan, Moh
- Date
- 2012
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/65991
- Identifier
- vital:6284
- Identifier
-
https://doi.org/10.4049/jimmunol.1101040
- Identifier
- ISSN:0022-1767
- Abstract
- We treated mice with 5-fluorouracil (5-FU) to isolate a quiescent and undifferentiated mesenchymal stromal cell (MSC) population from the bone marrow. We examined these 5-FU–resistant MSCs (5-FU–MSCs) free from hematopoietic components for CFU fibroblasts (CFU-Fs) and assessed their immunosuppressive potential in vitro and in vivo. We differentiated fibroblastic CFU-Fs (Fibro–CFU-Fs) from mixed CFU-Fs, based on the absence of in situ expression of CD11b and CD45 hematopoietic markers, as well as on their differentiation capacity. Fibro–CFU-Fs were associated with increased numbers of large-sized Fibro–CFU-Fs (≥9 mm2) that displayed enhanced capacity for differentiation into adipogenic and osteogenic mesenchymal lineages. Administration of these 5-FU–resistant CD11b−CD45− MSCs 6 d after myelin oligodendrocyte glycoprotein (MOG) immunization completely remitted MOG-induced experimental autoimmune encephalomyelitis after initial development of mild disease. The remission was accompanied by reduced CNS cellular infiltration and demyelination, as well as a significant reduction in anti-MOG Ab and splenocyte proliferation to MOG. MOG-stimulated splenocytes from these mice showed elevated levels of Th2 cytokines (IL-4, IL-5, and IL-6) and decreased IL-17. Compared with untreated MSCs, 5-FU–MSCs demonstrated potent immunosuppression of Con A-stimulated splenocytes in vitro, even at a 1:320 MSC/splenocyte ratio. Immunosuppression was accompanied by elevated IL-1ra, IL-10, and PGE2. Blocking IL-1ra, IL-10, and PGE2, but not IL-6, heme oxygenase-1, and NO, attenuated 5-FU–MSC–induced immunosuppression. Together, our findings suggested that immunosuppression by 5-FU-MSC is mediated by a combination of elevated IL-1ra, IL-10, and PGE2, anti-inflammatory Th2 cytokines, and decreased IL-17. Our findings suggested that 5-FU treatment identifies a population of potently immunosuppressive 5-FU–MSCs that have the potential to be exploited to remit autoimmune diseases.
- Relation
- Journal Of Immunology Vol. 188, no. 5 (2012), p. 2207-2217
- Rights
- Copyright American Association of Immunologists
- Rights
- This metadata is freely available under a CCO license
- Subject
- 1107 Immunology
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