TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis

• DOI: 10.1371/journal.pone.0220756
• Publication Date: 2020-02-10T13:24:01Z
• Authors: Ju-Hyun An; Qiang Li; Min-Ok Ryu; A-Ryung Nam; Dong-Ha Bhang; Yun-Chan Jung; Woo-Jin Song; Hwa-Young Youn
• Keywords: Inflammation; 0301 basic medicine; 0303 health sciences; Science; Macrophages; Q; Dextran Sulfate; R; Cell Count; Mesenchymal Stem Cells; Colitis; T-Lymphocytes, Regulatory; 3. Good health; Extracellular Vesicles; Mice; 03 medical and health sciences; Dogs; Medicine; Animals; Cytokines; Cell Adhesion Molecules; Research Article

AbstractMesenchymal stem/stromal cell (MSC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms have not been fully elucidated. We hypothesize that the tumor necrosis factor-α-stimulated gene/protein 6 (TSG-6) in EVs is a key factor influencing the alleviation of colitis symptoms. DSS-induced colitis mice (C57BL/6, male, n = 6-8/group) were intraperitoneally administered EVs (100 ug/mice) on day 1, 3, and 5; colon tissues were collected on day 10 for histopathological, qRT-PCR, western blot, and immunofluorescence analyses. In mice injected with EV, inflammation was alleviated. Indeed, EVs regulated the levels of pro- and anti-inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, IL-6, and IL-10 in inflamed colons. However, when injected with TSG-6 depleted EV, the degree of inflammatory relief was reduced. Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs in the colon.