Regulation of Immunity via Multipotent Mesenchymal Stromal Cells

Abstract

Immune cells responsible for inflammation development are involved in tissue damage caused by wounding and various pathologies. Control of immune cell activation could be of significant benefit for regenerative medicine and the treatment of patients with autoimmune and degenerative diseases. It is a proven fact that MCSs (multipotent mesenchymal stromal cells) are capable of suppressing immune responses via the inhibition of dendritic cell maturation and via the restraining of the T, B, and NK cell function in the course of autoimmune diseases and various forms of inflammation. MSCs can be isolated easily from almost every type of tissue or organ and subsequently expandedin vitro. These cells are self-renewable and can be differentiated into various cell types of mesenchymal lineage. The current review contains a collection and critical analysis of data regarding the molecular mechanisms responsible for cross-talk between immune cells and MSCs. Some of these mechanisms can be used for the development of new practical approaches for the treatment of autoimmune diseases.

Keywords: autoimmune disease; immune suppression; immune system; inflammation; multipotent mesenchymal stromal cells; regeneration.

Fig. 1

Main events following damage to inflammatory/wound tissue and the involvement of immune cells. The effect of MSCs on particular steps is shown with arrows in the case of positive influence; and with blunt-end arrows, in the case of negative (inhibitory) influence.

Fig. 2

Schematic representation of the key factors involved in immunosuppression stimulation by MSC (on the left) and soluble effector molecules mediating the inhibitory effect of MCS on T cell function (on the right).

Fig. 3

Spectrum of MSC-mediated immunosuppression cellular targets. MSC immunosuppression inducers are presented in the frame on the left-hand side, the main molecules – mediators of suppression – on the right-hand side. MSCs induce neutrophil apoptosis, inhibit dendritic cell maturation and secretion of proinflammatory cytokines (IFN-γ, IL-12, TNF-α), slow down proliferation and B-cell differentiation towards plasma cells, decrease immunoglobulin secretion, limit division of NK, CD4 and CD8 T cells, and limit the secretion of proinflammatory cytokines and the maturation of cytotoxic T cells from CD8 T cells. At the same time, MSCs stimulate IL-10 production by dendritic and regulatory T cells and boost expansion of regulatory T cells. The arrows indicate the positive effect of MSCs on cell function, whereas the blunt-end arrows indicate the negative effect of MSCs.