Artikel
Are mesenchymal stem cells (MSCs) able to control pro-inflammatory T cells?
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Veröffentlicht: | 29. August 2016 |
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Gliederung
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Background: Pro-inflammatory T-cells and their cytokines play an important role in chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA). Some studies have shown immune regulation by MSCs. MSCs are multipotent cells able to differentiate into cells of the mesenchymal linage. To evaluate the capacity of MSCs to regulate T-cell differentiation and pro-inflammatory cytokine production naïve and non-naïve CD4 T-cells were isolated from peripheral blood of RA patients and healthy donors (HD).
Methods: Naïve and non-naïve CD4+ T-cells were stimulated with a Th17-inducing cytokine cocktail in the presence or absence of MSCs. Expression of CD45RA and CD27, chemokine receptors (CXCR3, CCR6, CCR5), and the intracellular production of IFNgamma, IL-17, and IL-9 were determined by flow cytometry. IL-9 was determined in supernatants by ELISA.
Results: Non-naïve T-cells from RA patients produced higher amounts of IFNgamma and IL-17 compared to HD. Naïve and non-naïve CD4+ T-cells reduced the production of intracellular IFNgamma, IL-17 and IL-9 in the presence of MSC in RA patients and HD. Expression of CXCR3 and CCR6 was downregulated in both subpopulations in co-culture with MSCs, with no significant changes in CCR5. In co-culture supernatants of naïve and non-naïve CD4+ T-cells with MSCs, IL-9 was lower compared to culture without MSCs.
Conclusion: Our findings indicate a significant immunomodulatory property of MSCs to modulate differentiation and the cytokine producing ability of naïve and non-naïve CD4+ T cells in vitro in both RA patients and HD. The potential therapeutic use of MSCs to control inflammation in RA may be further investigated from a clinical viewpoint.