Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review

Table 1 Immune modulation of extracellular vesicles in autoimmune related diseases

Disease	EVs	Expression	MSC-EVs source/ Target molecules	Target immune cells	Pathway(s) involved	Ref.
RA	MSC derived exosomal miR-150-5p	Down	Bone marrow derived MSC-EVs/MMP 14 and VEGF	Macrophages	TGF-β pathway	Chen et al[80]
	Exosome-encapsulated miR-548a-3p	Down	TLR4	Macrophages	MiR-548a-3p/TLR4/NF-κB axis	Wang et al[81]
	Exosome-encapsulated miR-6089	Down	TLR4	Macrophages	TLR4/NF-κB signaling pathway	Xu et al[82]
	Exosome-derived lncRNA Hotair	Up	MMP-2 and MMP-13	Macrophages	-	Song et al[83]
	Exosomal miR-17	Up	TGFBR II	T cells	-	Wang et al[84]
	MicroRNA-155	Up	SHIP-1	Macrophages	-	Kurowska-Stolarska et al[85]
	MicroRNA-146	Up	-	Macrophages, T cells, B cells	-	Nakasa et al[86]
SLE	Exosomal miR-26a	Up	Podocyte proteins, actin family members, and intermediate filaments	Podocytes	-	Ichii et al[99]
	Exosomal miRNA-146a	Up	-	-	Interferon-γ pathway	Perez-Hernandez et al[100]
pSS	EV derived LCN2	Up	TNF-α	B cells	TNF-α signaling	Aqrawi et al[107]
	EV derived APMAP	Up	TNF-α	B cells	TNF-α signaling	Aqrawi et al[107]
	EV derived CPNE1	Up	TNF-α	B cells	TNF-α signaling	Aqrawi et al[107]
IBD	MSC-EVs	Up	Bone marrow derived MSC-EVs	Macrophages	JAK1/STAT1/STAT6 signaling pathway	Cao et al[113]
Breast cancer	Exosomal PD-L1	Down	PD-1	T cells	PD-L1/ PD-1 pathway	Yang et al[120]
Lung cancer	EV derived miR-103a	Up	Lung cancer cell derived EVs/PTEN	Macrophages	PI3K/ AKT and STAT3 axis	Hsu et al[121]
Pancreatic cancer	Exosomal miR-301a-3p	Up	PTEN	Macrophages	PI3Kγ signaling pathway	Wang et al[122]
GVHD	MSC-EVs	Up	T cell derived EVs	-	-	Park et al[126]

RA: Rheumatoid arthritis; SLE: Systemic lupus erythematosus; pSS: Primary Sjgren's syndrome; IBD: Inflammatory bowel diseases; GVHD: Graft-versus-host disease; MSC: mesenchymal stem cell; EV: Extracellular vesicle; MSC-EV: Mesenchymal stem cell derived extracellular vesicle; MMP: Matrix metalloproteinase; VEGF: Vascular endothelial growth factor; TGFBR II : Transforming growth factor beta receptor II; SHIP-1: Src homology 2-containing inositol phosphatase-1; PD-1: Programmed death-1; PD-L1: PD-1 ligand; LCN2: Neutrophil gelatinase-associated lipocalin; APMAP: Adipocyte plasma membrane-associated protein.