Interferon-γ-Treated Mesenchymal Stem Cells Modulate the T Cell-Related Chemokines and Chemokine Receptors in an Animal Model of Experimental Autoimmune Encephalomyelitis.

Abstract

Background: Mesenchymal stem cells (MSCs) modulate immune responses, and their immunomodulatory potential can be enhanced using inflammatory cytokines. Here, the modulatory effects of IFN-γ-licensed MSCs on expression of T cell-related chemokines and chemokine receptors were evaluated using an experimental autoimmune encephalomyelitis (EAE) model.

Material and methods: EAE was induced in 3 groups of C57bl/6 mice and then treated with PBS, MSCs and IFN-γ-treated MSCs. The EAE manifestations were registered daily and finally, the brain and spinal cords were isolated for histopathological and gene expression studies.

Results: The clinical scores were lowered in MSCs and IFN-γ-licensed MSCs groups, however, mice treated with IFN-γ-licensed MSCs exhibited lower clinical scores than MSCs-treated mice. Leukocyte infiltration into the brain was reduced after treatment with MSCs or IFN-γ-licensed MSCs compared to untreated group (P<0.05 and P<0.01, respectively). In comparison with untreated EAE mice, treatment with MSCs reduced CCL20 expression (P<0.001) and decreased CXCR3 and CCR6 expression (P<0.02 and P<0.04, respectively). In comparison with untreated EAE mice, treatment with IFN-γ-licensed MSCs reduced CXCL10, CCL17 and CCL20 expression (P<0.05, P<0.05, and P<0.001, respectively) as well as decreased CXCR3 and CCR6 expression (P<0.002 and P<0.02, respectively), whilst promoting expression of CCL22 and its receptor CCR4 (P<0.0001 and P<0.02, respectively). In comparison with MSC-treated group, mice treated with IFN-γ-licensed MSCs exhibited lower CXCL10 and CCR6 expression (P<0.002 and P<0.01, respectively), whereas greater expression of CCL22 and CCR4 (P<0.0001 and P<0.01, respectively).

Conclusion: Priming the MSC with IFN-γ can be an efficient approach to enhance the immunomodulatory potential of MSCs.