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

Abstract

Tightly controlled communication among the various resident and recruited cells in the intestinal tissue is critical for maintaining tissue homeostasis, re-establishment of the barrier function and healing responses following injury. Emerging evidence convincingly implicates extracellular vesicles (EVs) in facilitating this important cell-to-cell crosstalk by transporting bioactive effectors and genetic information in healthy tissue and disease. While many aspects of EV biology, including release mechanisms, cargo packaging, and uptake by target cells are still not completely understood, EVs contribution to cellular signaling and function is apparent. Moreover, EV research has already sparked a clinical interest, as a potential diagnostic, prognostic and therapeutic tool. The current review will discuss the function of EVs originating from innate immune cells, namely, neutrophils, monocytes and macrophages, as well as intestinal epithelial cells in healthy tissue and inflammatory disorders of the intestinal tract. Our discussion will specifically emphasize the contribution of EVs to the regulation of vascular and epithelial barrier function in inflamed intestines, wound healing, as well as trafficking and activity of resident and recruited immune cells.

Keywords: barrier; epithelial cells; exosomes; inflammation; macrophages; microRNAs; microparticles; neutrophils; vesicles; wound healing.

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).

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.