Yang Xiaojun, Meng Song, Jiang Hong, Chen Tao, Wu Wenxi
Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Scand J Gastroenterol. 2010 Oct;45(10):1168-77. doi: 10.3109/00365521.2010.490596.
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.
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.
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.
The results suggest that IL-10-exosomes treatment can suppress acute TNBS-induced colitis and may offer a promising new therapeutic strategy for IBD.
炎症性肠病（IBD）主要指克罗恩病和溃疡性结肠炎，其特征为胃肠道的慢性炎症。最近的报告表明，源自白细胞介素10（IL-10）处理的骨髓来源树突状细胞（DCs）的外泌体可降低小鼠中已建立的胶原诱导性关节炎（CIA）的发病率和严重程度。基于IL-10在正常黏膜免疫发育中的重要作用，我们研究了源自经IL-10处理的DCs（称为IL-10-外泌体）的外泌体是否能抑制三硝基苯磺酸（TNBS）诱导的结肠炎。
我们使用大鼠TNBS诱导的结肠炎模型来研究IL-10-外泌体在体内的治疗潜力。更具体地说，将TNBS直肠灌肠给予Wistar大鼠，并在第3天腹腔注射IL-10-外泌体。
在主要组织相容性复合体II类（MHC II）水平高且共刺激分子和膜结合IL-10表达水平低的情况下，IL-10-外泌体处理显著降低了TNBS诱导的结肠炎的所有分析的临床、宏观和组织病理学参数。IL-10-外泌体的治疗效果与结肠组织中IL-2、IFN-γ和TNF-α的mRNA表达下调有关。重要的是，用IL-10-外泌体处理导致结肠组织中IL-10mRNA表达以及结肠固有层中的调节性T细胞（Tregs）明显上调。
结果表明，IL-10-外泌体处理可抑制急性TNBS诱导的结肠炎，并可能为IBD提供一种有前景的新治疗策略。
