Table 1.

Summary of Treg-derived EVs researches focusing on autoimmune diseases and transplantation models

Disease	Animal model/patient	EV source	EV content	In vitro outcome	In vivo outcome	Refs.
Kidney allograft	BN (RT1n) rat to Lewis (RT11) rat	MLN-derived Tregs	NS	↓ T cell proliferation	Lagging acute allograft rejection	[27]
Colitis and systemic Inflammation	Rag2Neg/Neg mice	LO-derived Tregs	CD63, CD9, CD81 premature and mature miRNAs (including miR-466 family, miR-195, miR-16, Let-7d), T (h1) suppressive mRNA transcripts	↓ Th1 cell proliferation and IFNγ secretion	Suppression and prevention of systemic disease	[28]
Kidney allograft	BN (RT1n) rat to Lewis (RT11) rat	DnIKK2-Tregs	CD63, TSG101, iNOS, specific miRNAs (including miR-503, miR-330, miR-293, miR-297c, miR-207, miR-9 & miR-484)	↓ T cell proliferation, cell cycle arrest, apoptosis induction, naive to Treg cell conversion	Protracting kidney allograft survival	[109]
Relapsing–remitting multiple sclerosis	Human blood	PBMC-derived Tregs	CD63	Attenuated inhibition of conventional T cell proliferation and apoptosis	NS	[110]
Skin xenograft	Human to (Rag)2Neg/NegγcNeg/Neg (BRG) BALB/c mice	Human PBMC-derived Tregs	CD63, CD81, CD25, CD39, CCR4, CD4, CTLA-4, HSP90AB1, actin and tubulin, several miRNAs (including miR-142-3p & miR-150-5p)	↓ T cell proliferation, ↓ IFNγ, IL-2 and IL-6 secretion, ↑ IL-10 & IL-4 levels	Protracting skin xenograft survival	[79]

EV extracellular vesicle, BN Brown Norway, MLN mesenteric lymph node, Rag2 recombination-activating gene 2, LO lymphoid organ, miRNA microRNA, mRNA messenger RNA, Th T helper, DnIKK2 dominant-negative form of IKK2, TSG101 tumor susceptibility gene 101, iNOS inducible nitric oxide synthase, PBMC peripheral blood mononuclear cell, CTLA-4 cytotoxic T lymphocyte-associated antigen-4, HSP heat shock protein, IFNγ interferon gamma ↓: decrease, ↑: increase, NS not specified