Table 1.
Mechanisms of mesenchymal stem cell (MSC) immunosuppression on immune cells. Recapitulation of recent reports describing the known mechanisms via which MSCs exert suppressive function to different immune populations.
| Target Cell | Involved Mechanism | Observed Effect | References |
|---|---|---|---|
| Innate Cells | |||
| DCs | TGF-β, HGF, EVs | ↓MHC-II, CD86, CD40; ↑phagocytic function; ↓IL-6, IL-12, TNF-α, IFN-α; ↑IL-10, TGF-β |
[50,51,52,53,54] |
| Macrophages | TGF-β, iNOS, mitochondrial transfer, EVs | ↓CD86; ↑phagocytic function, ↓IL-6, IL-8, TNF-α, IL-1β; ↑IL-10, TGF-β; ↑M2 type polarization |
[55,56,57,58,59,60,61,62] |
| NK cells | IDO, PGE2, EVs | ↓IFN-γ; ↓cytotoxic activity, proliferation | [63,64,65,66] |
| Neutrophils | TGF-β, EVs | ↓CRAMP and MPO messenger RNA (mRNA), ↓IL-17 | [52,57,61,67] |
| ILC | PGE2, IL-7 | ↑IL-22; ↑proliferation | [68] |
| Adaptive Cells | |||
| B cells | PD-1, IDO, TGF-β, EVs | ↓IgG production; ↓CD69, CD83, CD86; ↓IL-4 mRNA; ↓proliferation, plasmablast differentiation; ↑IL-10 | [66,69,70,71,72,73,74,75] |
| Th1 cells | PD-1, IDO, Fas, IL-6, TGF-β, IL-1Ra, EVs, mitochondrial transfer | ↓IFN-γ, IL-1β, TNF-α; ↑apoptosis; ↓proliferation; differentiation | [52,58,67,76,77,78,79,80,81,82,83,84,85] |
| Th2 cells | IL-6, EVs | ↑differentiation; ↑IL-4, IL5; ↓IL-4, IL-5, IL-13 | [67,76,86,87,88,89] |
| Th17 cells | PGE2, Fas, IDO, IL-6, TGF-β, IL-1Ra, EVs, mitochondrial transfer | ↓IL-17, IL-22; ↑apoptosis; ↓proliferation; differentiation; ↑interconversion to Treg cells. | [54,58,67,75,76,77,78,79,81,82,83,84,90,91,92,93,94,95,96,97,98,99] |
| Regulatory T (Treg) cells | PGE2, Fas, IDO, IL-6, iNOS, TGF-β, IL-1Ra, EVs, mitochondrial transfer | ↑PD-1, ↑IL-10, TGF-β; ↑proliferation; differentiation; ↑conversion from Th17 cells. | [54,58,59,66,67,75,76,77,78,79,80,81,82,85,90,91,92,93,94,96,97,98,99,100] |
CRAMP: cathelicidin-related antimicrobial peptide; DCs: dendritic cells; EVs: extracellular vesicles; HGF: hepatocyte growth factor; IDO: indoleamine 2,3-dioxygenase; IFN: interferon; IgG: immunoglobulin G; IL: interleukin; ILC: innate lymphoid cells; iNOS: inducible nitric oxide synthase; IL-1Ra: IL-1 receptor agonist; MHC-II: class II major histocompatibility complex; MPO: myeloperoxidase; PD-1: programmed cell death-1; PGE2: prostaglandin E2; TGF-β: transforming growth factor-β; Th: T helper; TNF-α: tumor necrosis factor-α. ↑: upregulation; ↓: downregulation.