Mesenchymal stem cells: a friend or foe in immune-mediated diseases

Mesenchymal stem cells (MSCs) are adult, self-renewable, multipotent cells that can be found in almost all postnatal tissues. Because of their capacity for self-renewal and differentiation into tissues of mesodermal origin and due to their immunomodulatory ability, MSCs are used in many preclinical and clinical studies as possible new therapeutic agents for the autoimmune or degenerative diseases treatment. In dependence of inflammatory environment to which they are exposed to, MSCs adopt immunosuppressive or pro-inflammatory phenotype. In the presence of high levels of pro-inflammatory cytokines or through activation of Toll-like receptor (TLR)-3, MSCs adopt an immune-suppressive phenotype and suppress the proliferation, activation and effector function of professional antigen presenting cells (dendritic cells, macrophages, B lymphocytes), T lymphocytes, NK cells, NKT cells, and neutrophils. During the early phase of inflammation, through TLR4 activation and in the presence of low levels of inflammatory cytokines, MSCs adopt a pro-inflammatory phenotype, promote neutrophil and T cell activation and enhance immune response. Here we review the current findings on the immunoregulatory plasticity of MSCs involved in regulation of immune response.