PT  - JOURNAL ARTICLE
AU  - Ju-Hyun An
AU  - Woo-Jin Song
AU  - Qiang Li
AU  - Min-Ok Ryu
AU  - A-Ryung Nam
AU  - Dong-Ha Bhang
AU  - Yun-Chan Jung
AU  - Hwa-Young Youn
TI  - TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis
AID  - 10.1101/714931
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 714931
4099  - http://biorxiv.org/content/early/2019/07/25/714931.short
4100  - http://biorxiv.org/content/early/2019/07/25/714931.full
AB  - Mesenchymal 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.