Immunomodulatory effects of adipose-derived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets.

It has been proposed that the immunomodulatory properties of mesenchymal stem cells (MSCs) play a crucial role in establishing and leading T lymphocytes, especially Th cell subsets, toward different functional subsets. To determine the effect of the immunomodulatory and regulatory functions of adipose-derived MSCs (AD-MSCs) on C57BL/6 spleen-isolated mononuclear cells (Spleen-MNCs), the gene expression of well-known effector and regulatory Th cell-related transcription factors, i.e., t-bet, GATA-3, Ror-γt and Foxp3, and their related cytokines, i.e., IFN-γ for Th1 cells, IL-4 for Th2 cells, IL-17 for Th17 cells and IL-10 and TGF-β for regulatory T cells, was studied using a co-culture condition system. The proliferation index of Spleen-MNCs was analyzed using a cell proliferation assay kit that utilized the CFSE staining method. Our findings indicate that AD-MSCs greatly impact the up-regulation of immunomodulatory cytokines, such as TGF-β (p<0.001), and the down-regulation of inflammatory cytokines, such as IFN-γ (p<0.005), and transcription factors, such as t-bet (p<0.001). Considering the immunomodulatory effects of MSCs in the differentiation of Th cell subsets, understanding and harnessing this property of MSCs could be a powerful strategy in the treatment of inflammatory autoimmune diseases such as multiple sclerosis.