Re-establishing immune tolerance in multiple sclerosis: focusing on novel mechanisms of mesenchymal stem cell regulation of Th17/Treg balance

Table 1 The major soluble factors that regulate Th17/Treg homeostasis in MSCs

The type of soluble factors	Sources of MSCs	In vitro or in vivo	Effects of MSCs on Th17/Treg	Authors	References
sTNFR1	Skin	In vivo	Inhibit RORγt expression and Th17 cell production, and ultimately, significantly improving clinical scores in EAE	Ke et al.	[84]
CCL2	BM	In vivo	Bind to CCR2 on the surface of Th17 cells, inhibits STAT3 phosphorylation in Th17 cells, and reduce the production of Th17 cells in EAE mice	Rafei et al.	[86]
IL-17RA	AD	In vivo	Inhibit the proliferation and differentiation of Th17 cells and enhance the expression levels of other immunosuppressive mediators such as: VCAM1, ICAM1 and PD-L1	Kurte et al.	[87]
IL-37	H-hPDLSCs-CM	In vivo	Binds to phosphorylated Smad-3 to form IL-37-Smad3 complex, reducing secretion of pro-inflammatory factors such as: IL-17, IL-1α, IL-6, TNF and CXCL2	Giacoppo et al.	[89]
IDO	Murine endometrial-derived MSCs	In vivo	Reduced Th1 and Th17 cells both in the periphery and CNS, whereas IL-10-secreting T CD4 + lymphocytes were increased, ultimatly suppressing EAE scores	Polonio et al.	[92, 93]
PGE2	BM	In vitro	Inhibit IL-17A secretion and Th17 cell production via an EP4-mediated, contact-dependent mechanism	Duffy et al.	[95]
TGF-β	Unknown	In vitro	Inhibit Th17 cell production mediated by dendritic cells, induce the differentiation of conventional CD4 CD25⁺⁺⁻ T cells into Foxp3 Treg cells	Favaro et al.	[94]

AD adipose tissue, BM bone marrow, H-hPDLSCs-CM human periodontal ligament stem cells conditioned medium, MSCs mesenchymal stem cells, EAE experimental autoimmune encephalomyelitis, sTNFR1 soluble TNF receptor 1, IDO indoleamine 2, 3-dioxygenase, PGE2 prostaglandin E2, EP4 PGE2 receptor 4, VCAM vascular cell adhesion protein, ICAM1 intercellular adhesion molecule, PD-L1 programed death ligand 1

ISSN: 1479-5876