Extracellular vesicles regulate immune responses and cellular function in intestinal inflammation and repair

Figures & data

Figure 1. Characterization of PMN-derived EVs. (A-B) PMNs were stimulated with fMLF (1μM) to produce EVs. EVs were isolated by serial centrifugation and analyzed by transmission electron microscopy. (A) A representative EV with the size of exosomes (< 100 nm). (B) A representative microparticle/ectosome with the size of ∼600 nm. (C) PMNs (immunolabeled for CD11b, red and myeloperoxidase, green) release myeloperoxidase-containing EVs (shown by arrows) following adhesion to and migration across IECs (surface stain, blue).

Table 1. A summary of miRNAs that have been shown to be transported by immune, epithelial, and endothelial cell-derived EVs and their contribution to cellular signaling and intestinal homeostasis.

	Target genes	Effects	Reference
miR-146	TLR4, TRAF6, IκBα	– Suppressed NFκB signaling	87, 88, 89, 125, 14
		– Increased cell survival.	2
		– Increased monocytic IL-10 production
		– Decreased IL-8 and CCL5 production
miR-21	RhoB, Cdc42	– Increased colonic epithelial permeability.	82, 83
	PTEN, PDCD4	– Modulate PTEN/ PI3K/ Akt axis.	80
		– Decreased tight junction proteins, i.e. occluding and E-cadherin
		– Increased IL-6 and IL-8 production
miR-29a	Glutamine synthetase, integrin-β1, claudin-1	– Impaired intestinal barrier functions.	77, 78
	LRP6, HuR	– G1-phase arrest and impaired proliferation
	Mcl-1	– -IEC apoptosis
miR-16	Cingulin, claudin-2, occludin	– Impaired tight junction integrity	90, 91
		– Altered cytokine secretion by degradation of TNFα, IL-8, and IL-6 mRNAs.
miR-223	IKKα	– Suppressed NFκB signaling	110, 111
	STAT3	– Decreased IL-6 and IL-1β production
	NLRP3	– Decreased NLRP3 inflammasome activity
	ARNT	– - Suppressed AHR-mediated Notch signaling
miR-155	SOCS1	– Increased cytokine production of IL-6/ IL-8	124, 128
		– Upregulation of VCAM1 and ICAM1, followed by Increased adhesion of monocytes/T-cells to endothelial cells
miR-206	A3AR	– Increased NFκB/p65 signaling	138, 139
		– Increased IL-8/ IL-1β secretion
		– Increased DSS-induced colitis severity
miR-141	CXCL12β	– Reduced leukocyte trafficking	141
		– Alleviated experimental colitis
miR-221	p27	– Increased cell growth	143
	DDIT4	– Dysregulation of mTOR signaling
	TIMP2	– Increased MMP-2/MMP-9 expression followed by remodeling of junctions and ECM
miR-320	NOD2	– Suppressed NFκB/p65 signaling	143
		– Decreased cytokine production

Figure 2. EV content and regulation of intestinal homeostasis. Schematic of EV release by various gut resident and recruited cells, as well as EV-mediated transport of proteins, lipids, and miRNAs to regulate cell function and intestinal homeostasis.

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