Xiaojun Yang1, Song Meng, Hong Jiang, Tao Chen, Wenxi Wu. 1. Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Abstract
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. MATERIAL AND 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.
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. MATERIAL AND METHODS: We used the ratTNBS-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.
Authors: Shuji Mitsuhashi; Linda Feldbrügge; Eva Csizmadia; Masato Mitsuhashi; Simon C Robson; Alan C Moss Journal: Inflamm Bowel Dis Date: 2016-07 Impact factor: 5.325
Authors: Doru T Alexandrescu; Thomas E Ichim; Neil H Riordan; Francesco M Marincola; Constantin A Dasanu Journal: J Immunother Date: 2011-10 Impact factor: 4.456