Table 2: Anti-inflammatory mechanisms of MSCs

From: Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine

Target cellMechanismPrimary effectSecondary effect
Dendritic cellsPGE2/direct contact↓ TNF-α, IL-12, differentiation and activationImpairs effect on resting NK cells
↓ T-cell proliferation
↓ INF-γ by TH1 cellsa
 PGE2, IL-6, IL-8 and SDF-1↑ IL-10↑ IL-4 by TH2 cellsa
Immature Dendritic cellsPGE2↑ IL-10↑ Treg production,
↑ IL-10 by Treg cells
T cells (CD4+, helper T cells)PGE2, IDO, HGF, TGF-β1 and NO↓ CD4+ T-cell proliferation by S-phase entry block and Go/G1 phase arrest
Inhibits T-cell functions
↓ B-cell proliferation
↓ Ig antibody production by B cells
 IL-10Inactivate TH1 cells 
T cells (CD8+, cytotoxic T cells)sHLA-G5↓ cytotoxicity 
Treg cellsIL-10↑ Treg production
↑ IL-10 by Treg cells
 
 sHLA-G5↓ Treg differentiation 
B cellsPGE2, HGF, TGF-β1, IDO, NO and PD-L1↓ B-cell proliferation by Go/G1 phase arrest
↓ Ig antibody production by B cells,
↓ B-cell chemotaxis
 
NK cellsPGE2, IDO, sHLA-G5, HGF, TGF-β1↓ INF-γ
↓ NK cell proliferation
↓ cytotoxicity
 
MonocytesPGE2↓ Monocyte proliferation by Go/G1 phase arrest
↓ Monocyte difference to DC
 
MacrophagesIL-6↓ TNF-α 
 TSG-6↓ NF-kB↓ TNF-α and IL-1
↓ MMP synthesis
 PGE2Converts M1 (pro-inflammatory) type to M2 (anti-inflammatory) type macrophages↓ IL-10
↓ IL-12
↓ TNF-α
NeutrophilsIL-6↓ respiratory burst
↓ apoptosis
 
No specific targetVEGFPro-angiogenicIncreased nutrient, O2 and waste transport
 IL-1RaAntagonizes IL-1 
 sTNF-RInhibits TNF-α production↓ T-cell proliferation,
↓ INF-γ by TH1 cellsa
  1. Abbreviations: HGF, hepatocyte growth factor; HLA, human leukocyte antigen; IDO, indoleamine 2,3-dioxygenase; IL-1Ra, IL-1 receptor antagonist; INF, interferon; MMP, matrix metalloproteinase; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cell; NK, natural killer; NO, nitrous oxide; PD-L1, programmed cell death ligand-1; PGE2, prostaglandin 2; SDF-1, stromal cell-derived factor-1; sTNF-R, soluble TNF-α receptor; TGF, transforming growth factor; TNF, tumor necrosis factor; TSG, tumor necrosis alpha-stimulating gene; VEGF, vascular endothelial growth factor.
  2. aPromotes TH1TH2 T-cell transition.