Delivery of IL-12p40 ameliorates DSS-induced colitis by suppressing IL-17A expression and inflammation in the intestinal mucosa
Delivery of IL-12p40 ameliorates DSS-induced colitis by suppressing IL-17A expression and inflammation in the intestinal mucosa
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DOI：
10.1016/j.clim.2012.06.009
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发表时间：
2012-09-01
影响因子：
8.6
通讯作者：
Sung, Young-Chul
中科院分区：
文献类型：
--
作者：
Kim, Doo-Jin;Kim, Kwang-Soon;Sung, Young-Chul
IL-12 p40同源二聚体是IL-12和IL-23的天然拮抗剂，IL-12和IL-23分别是Th 1和Th 17免疫应答所需的强效促炎细胞因子。据报道，Th 17应答与炎症性肠病（IBD）有关，IBD是一种慢性消化系统疾病，发病率稳步上升。在此，我们研究了通过重组腺病毒（rAd/IL-12 p40）或间充质干细胞（MSC/IL-12 p40）递送的IL-12 p40在葡聚糖硫酸钠盐（DSS）诱导的结肠炎模型中的作用。注射rAd/IL-12 p40或MSC/IL-12 p40有效地减轻结肠炎症状和组织损伤，导致存活率增加。此外，IL-12 p40递送抑制IL-17 A，但增强来自肠系膜淋巴结细胞的IFN-γ产生，支持IL-12 p40同型二聚体在体外优先抑制IL-23和在体内抑制Th 17应答。我们的研究结果表明，IL-12 p40递送通过抑制IL-17 A产生和肠粘膜炎症来改善DSS诱导的结肠炎，为IBD提供了有效的新治疗策略。(c)2012 Elsevier Inc. All rights reserved.
IL-12p40 homodimer is a natural antagonist of IL-12 and IL-23, which are potent pro-inflammatory cytokines required for Th1 and Th17 immune responses, respectively. It has been reported that Th17 response is involved in inflammatory bowel disease (IBD), a chronic disorder of the digestive system with steadily increasing incidence. Here, we investigated the effects of IL-12p40 delivered via recombinant adenovirus (rAd/IL-12p40) or mesenchymal stem cells (MSC/IL-12p40) in a dextran sulfate sodium salt (DSS)-induced colitis model. Injection of rAd/IL-12p40 or MSC/IL-12p40 efficiently attenuated colitis symptoms and tissue damage, Leading to an increased survival rate. Moreover, IL-12p40 delivery suppressed IL-17A, but enhanced IFN-gamma production from mesenteric lymph node cells, supporting the preferential suppression of IL-23 by IL-12p40 homodimer in vitro and the suppression of Th17 responses in vivo. Our results demonstrate that IL-12p40 delivery ameliorates DSS-induced colitis by suppressing IL-17A production and inflammation in the intestinal mucosa, providing an effective new therapeutic strategy for IBDs. (c) 2012 Elsevier Inc. All rights reserved.