Sca1LinCD117 Mouse Bone Marrow-Derived Mesenchymal Stem Cells Regulate Immature Dendritic Cell Maturation by Inhibiting TLR4-IRF8 Signaling Via the Notch-RBP-J Pathway.

Mesenchymal stem cells (MSCs) have a superior immunomodulatory capacity compared to other cells of the immune system, and they hold great promise for treating various immune disorders. However, their regulatory effects on the maturation of immature dendritic cells (imDCs) are not fully understood. In this study, we show that Sca-1LinCD117MSCs restrain the lipopolysaccharide-stimulated maturation transition of imDCs cocultured without exogenous cytokines. The Notch signaling pathway plays a critical role in the process by controlling interferon regulatory factor 8 (IRF8) expression in an RBP-J-dependent manner. We observed a high degree of H3K27me3 modification mediated by SUZ12 and a relatively low degree of H3K4me3 modification regulated by WDR5 at the IRF8 promoter during coculture. These data reveal a possible mechanism by which Sca-1LinCD117MSCs modulate imDC maturation and further support the role of MSCs in treating immune disorders.