Mesenchymal stem cell-mediated immunosuppression via cytokine secretion (MSC-mediated immunosuppression (MSC-IS))

Mesenchymal Stem Cells (MSCs) are multipotent stromal cells capable of immunomodulation primarily through cytokine secretion and direct interaction with immune cells. Upon activation by inflammatory cytokines (e.g., IFN-γ, TNF-α), MSCs secrete soluble factors such as indoleamine 2,3-dioxygenase (IDO), transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2), nitric oxide (NO), and interleukin-10 (IL-10), which collectively suppress T and B cell proliferation, induce regulatory T cells, and shift monocytes/macrophages towards anti-inflammatory phenotypes[1][2][3][5]. Additionally, MSCs express surface molecules such as PD-L1 and Galectin-9, mediating immunosuppression via cell-to-cell contact. These mechanisms have been leveraged experimentally and clinically to treat inflammatory and autoimmune diseases, with ongoing research aimed at optimizing efficacy and safety[1][2][3][5][6]. However, this immunosuppressive effect is a functional attribute of MSCs and not a single molecular entity.

Other names

Mesenchymal stem cell immunosuppressionMSC immunomodulationMSC immunoregulationMSC cytokine-mediated effects

Secretion of immunosuppressive cytokines and soluble factors (e.g., IL-10, TGF-β1, PGE2, IDO, HO-1, TSG-6)[1][2][3][5] Induction of regulatory T cells (Tregs) Promotion of anti-inflammatory M2 macrophages Inhibition of adaptive immune cell proliferation through cell-cell contact (PD-L1, Gal-9, ICAM-1)