Delivery of IL-12p40 ameliorates DSS-induced colitis by suppressing IL-17A expression and inflammation in the intestinal mucosa

被引：32

作者：

Kim, Doo-Jin ^{[1
,2
]}

Kim, Kwang-Soon ^{[3
]}

Song, Mi-Young ^{[3
]}

Seo, Sang-Hwan ^{[2
]}

Kim, Su-Jin ^{[2
]}

Yang, Bo-Gie ^{[3
]}

Jang, Myoung-Ho ^{[3
,4
]}

Sung, Young-Chul ^{[3
]}

机构：

[1] KRIBB, Viral Infect Dis Res Ctr, Taejon 305806, South Korea

[2] POSTECH, Div Mol & Life Sci, Pohang 790784, South Korea

[3] POSTECH, WCU, Div Integrat Biosci & Biotechnol, Pohang 790784, South Korea

[4] Osaka Univ, WPI Immunol Frontier Res Ctr, Osaka, Japan

来源：

CLINICAL IMMUNOLOGY | 2012年 / 144卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

IL-12p40; DSS-induced colitis; Inflammatory bowel disease (IBD); IL-17A; MESENCHYMAL STEM-CELLS; SODIUM-INDUCED COLITIS; SEVERE CROHNS-DISEASE; TNBS-INDUCED COLITIS; CD4(+) T-CELLS; BOWEL-DISEASE; P40; HOMODIMER; STIMULATORY FACTOR; INTERFERON-GAMMA; MICE;

D O I：

10.1016/j.clim.2012.06.009

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：190 / 199

页数：10

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