Exosomes derived from interleukin-10-treated dendritic cells can inhibit trinitrobenzene sulfonic acid-induced rat colitis.
OBJECTIVE
Inflammatory bowel disease (IBD), which mainly refers to Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. Recent reports have demonstrated that exosomes derived from interleukin-10 (IL-10)-treated bone marrow-derived dendritic cells (DCs) can reduce the incidence and severity of established collagen-induced arthritis (CIA) in mice. Based on the essential role of IL-10 in the development of normal mucosal immunity, we investigated whether exosomes derived from DCs treated with IL-10 (known as IL-10-exosomes) can suppress the trinitrobenzene sulfonic acid (TNBS)-induced colitis.


METHODS
We used the rat TNBS-induced colitis model to address the therapeutic potential of IL-10-exosomes in vivo. More specifically, a rectal enema of TNBS was administered to Wistar rats, and IL-10-exosomes were injected intraperitoneally on Day 3.


RESULTS
In the context of a high level of major histocompatibility complex class II (MHC II) and a low level of co-stimulatory molecule and membrane-bound IL-10 expression, IL-10-exosomes treatment substantially reduced all analyzed clinical, macroscopic, and histopathologic parameters of TNBS-induced colitis. The therapeutic effects of IL-10-exosomes were associated with a down-regulation mRNA expression of IL-2, IFN-γ and TNF-α in colon tissues. Importantly, treatment with IL-10-exosomes resulted in a pronounced up-regulation of IL-10mRNA expression in colon tissues and regulatory T cells (Tregs) in Colonic lamina propria.


CONCLUSIONS
The results suggest that IL-10-exosomes treatment can suppress acute TNBS-induced colitis and may offer a promising new therapeutic strategy for IBD.
Yang
Xiaojun
X
Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Meng
Song
S
Jiang
Hong
H
Chen
Tao
T
Wu
Wenxi
W
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D003713:Dendritic Cells; D004195:Disease Models, Animal; D055354:Exosomes / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000628:therapy; D007371:Interferon-gamma / Q000187:drug effects; D016753:Interleukin-10 / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000187:drug effects; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid