Table 1.

Immune-modulating effects of innate cell-derived EVs on other immune system cells or molecular targets.

Cell of origin	Cellular/molecular target	EV-surface proteins and content	Main biological effects	References
PMN	DC/macrophage	Phosphatidylserine Annexin 1 MPO CD11b/CD18 Lactoferrin Elastase	Reduced DC phagocytosis, maturation and capacity to stimulate T-cell proliferation; reduced production of pro-inflammatory cytokines and increased release of TGF β1 by DC and macrophage (tolerogenic profile)	(23, 24) (25, 26)
	T lymphocytes	CD11b/CD18 Annexin V Elastase	Reduced release of TNFα by naive and activated effector T cells; reduced IL2 secretion and CD25 expression by resting T helper cells	(27) (28) (29) (30) (31) (32)
	Cytokines/membrane receptors	Catepsin G Proteinase 3	Cleavage of cytokines and their membrane receptors	(33) (34)
	L-Arginine	Arginase-1	Reduced T-cell proliferation and function	(30)
	Neutrophil	LT B4 and enzymes for its synthesis; C5R1	PMN chemotaxis	(35) (36)
Macrophage	Macrophage and DC	p-MHC; Microbial and viral antigens; Hsp-70; IL1β; TNFα; CCL2-5; C3 fragments; Proteins of the leukotriene pathway IL 36y miR-223	Transfer of p-MHC, antigens and activating signals to DCs; DC maturation, activation and migration; release of Th1 - (M1 macrophages- derived EVs) or Th2-promoting cytokines (M2 macrophages-derived EVs)	(37) (38) (39) (40) (41) (42)
	PMN	Enzymes of the leukotriene biosynthesis	PMN chemotaxis	(43)
	T lymphocytes	IL1β TNFalfa and CCL2-5 proteins of the leukotriene pathway IL 36y	Increased T cell expansion and differentiation; induction of IFNy and IL 17 producing CD4+ T cells (T helper 17); inhibition of Treg	(40) (44) (45) (46) (35) (47)
	B lymphocytes	C3 fragments IL 36y	Increased B cell expansion and differentiation	(41, 48) (47)
DC	DC	TLR4 p-MHC; Costimulatory or inhibitory molecules; miRNA (miR-148a, miR 451)	Amplification of antigen spreading among APCs and antigen presentation to T lymphocytes	(49, 50) (17, 51) (52)
	PMN	Enzymes of the leukotriene biosynthesis	Neutrophil chemotaxis	(43)
	T lymphocytes	p-MHC; MHC II; Microbial or tumoral antigens; adhesion molecules (ICAM-1); costimulatory molecules (B7 family members)	Activation (mature DCs) or inhibition (immature DCs) of CD4/CD8 pos T lymphocytes	(4, 49) (53) (54) (55) (56)
	B-lymphocytes	Complement fragments, microbial or tumoral antigens		(20, 52)
MC	DC	p-MHC; FcϵRI Hsp 60, Hsp 70; PLA2, PLC, PLD; PGD2,PGE2	Transfer of p-MHC II and IgE-antigens complexes; antigens activation and DC maturation; generation of neolipid antigens	(51) (57) (58) (59) (60) (61)
	T lymphocyte	Proteases	Cytokine inactivation, T helper 2 induction	(51)
	B lymphocyte	CD 40	EVs binding; IL-10 competent B cells	(62)
Eosinophil	DC	MBP EPO	DC maturation; DC-driven Th2 response	(63) (64)
NK	T lymphocyte	Perforin FasL	Cell lysis	(65)