Mesenchymal Stem Cell Therapy for Cardiac Inflammation: Immunomodulatory Properties and the Influence of Toll-Like Receptors
Figure 1
Schematic overview of the interactions between MSC and the immune system. Mesenchymal stem cells influence the functioning of many immune cells. Via multiple possible pathways MSC suppress proliferation of both helper (TH) and cytotoxic T-cells (TC). In addition, differentiation to TH2 and regulatory T-cells is triggered, resulting in an anti-inflammatory environment. Maturation of immature dendritic cells (DC) is inhibited via IL-6, blocking upregulation of CD40, CD80, and CD86, which in turn can reduce T-cell activation. Monocytes are triggered by MSC to differentiate towards the M2 phenotype. Different mechanisms appear to be involved in this process, amongst which IDO, TGF-β, IL-10, and PGE2 are the most important ones. IL-10 produced by these M2 macrophages can boost the formation of, while reducing tissue migration of neutrophils. Neutrophils (polymorphonuclear granulocytes; PMN) are allowed a longer life span by MSC-derived IL-6, while ROS production is decreased. Natural killer cell (NK cells) proliferation is suppressed, as well as cytotoxic activity and cytokine secretion. B-cell proliferation is inhibited and the production of antibodies is reduced.
