Immunomodulatory properties of mesenchymal stem cells on innate and adaptive immunity. (A) MSC can modulate innate and adaptive immune cells by: (1) promoting repolarization of macrophages from type 1 to type 2 phenotype characterized by high levels of interleukin-10 secretion, which can block polymorphonuclear neutrophil influx into the injured tissue and prevent further damage; (2) interfering with dendritic cells differentiation, maturation, and function, skewing them toward a regulatory phenotype and decreasing their capacity to induce activation of T cells; and (3) impairing natural killer cells cytotoxic activity, cytokine production, and granzyme B release. However, recent studies suggest that the complex interplay between MSC and natural killer cells may depend on the surrounding milieu. (B) MSC can suppress T cell activation and proliferation and also decrease their response by shifting them from a T helper 1 to a T helper 2 immune response. MSC have been shown to (1) inhibit the differentiation of naive T cells into T helper 17 cells and prevent the secretion of proinflammatory cytokines by T helper 17 cells; and (2) promote induction of immunosuppressive T regulatory cells in part by reprogramming T helper 17 cells into T regulatory cells. DC = dendritic cell; HGF = hepatocyte growth factor; iDC = immature dendritic cell; IDO = indolamine 2,3-dioxygenase; IL-6 = interleukin-6; IL-10 = interleukin-10; M1 = type 1 phenotype; M2 = type 2 phenotype; MSC = mesenchymal stem cell; NK cell = natural killer cell; PGE2 = prostaglandin E2; PMN = polymorphonuclear neutrophil; TGFβ = transforming growth factor beta; Th = T helpers cell; Treg = T regulatory cell; TSG6 = tumor necrosis factor-stimulated gene 6.