Exosomes derived from T regulatory cells relieve inflammatory bowel disease by transferring miR‐195a‐3p

Abstract

Previous studies have demonstrated the therapeutic effects of regulatory T (Treg) cells on inflammatory bowel disease (IBD), but the mechanism is not well-understood. Exosomes have been proposed as a novel mechanism underlying the action of Tregs. This study aimed to investigate the therapeutic effects of exosomes secreted by Treg cells (Treg-Exo) on IBD and to explore the underlying mechanism. Treg-Exo was isolated from BALB/c mouse spleen mononuclear cells and then injected into a murine model of IBD induced by dextran sodium sulfate (DSS) exposure. A co-culture model of Treg-Exo and colonic epithelial YAMC cells in the presence of TNF-α was used to investigate the communication between Tregs and intestinal epithelial cells. in vitro results showed that Treg-Exo could be transferred to YAMC cells where Treg-Exo promoted cell proliferation and inhibited cell apoptosis. Animal experiments showed that Treg-Exo administration alleviated the DSS-induced IBD in mice. The therapeutic effects of Treg-Exo both in vitro and in vivo were eliminated when miR-195a-3p expression was inhibited in Treg-Exo. The pro-apoptotic Caspase 12 was identified as a direct target of miR-195a-3p. In conclusion, Treg-Exo alleviated the DSS-induced IBD through transferring miR-195a-3p.

Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease

“…Furthermore, EVs have been found to have immunosuppressive effects, such as suppressing the activation of DCs to induce immune tolerance and participating in regulatory T cell (Treg) activation [18] . Activated Treg also secretes exosomes containing miR-195-3p, targeting pro-apoptotic Caspase 12, to alleviate IBD in mice [70] . IEC-derived exosomes are crucial regulators among sections, mediating the modulation of resident immune cells.…”

Cell-to-Cell Communication by Host-Released Extracellular Vesicles in the Gut: Implications in Health and Disease

“…Liao et al (2020) showed that Treg exosomes alleviate the severity of IBD in mice challenged with dextran sodium sulphate by transferring miR-195a-3p into IECs. This miRNA inhibits apoptosis by targeting caspase-12, allowing cell proliferation and repair of the intestinal epithelial barrier [ 150 ].…”

Extracellular Vesicles: The Next Generation Theranostic Nanomedicine for Inflammatory Bowel Disease

“…133 Treg cell-derived exosomes can promote IEC proliferation, inhibit IEC apoptosis, and protect the intestinal barrier in IBD mouse model. 134,135 Granulocytic myeloid-derived exosomes can alleviate IBD by diminishing the proportion of Th1 cells, and promoting the expansion of Treg cells. 136 These immune cell-derived exosomes may be the new therapeutic intervention for IBD in the future.…”