title: Delivery of IL-12p40 ameliorates DSS-induced colitis by suppressing IL-17A expression and inflammation in the intestinal mucosa.
abstract: 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-γ 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.
authors: Division of Molecular and Life Sciences, POSTECH, Hyoja-dong, Pohang, Republic of Korea. golddj@kribb.re.kr
authors: Doo-Jin
authors: DJ
authors: Kim
authors: Kwang-Soon
authors: KS
authors: Kim
authors: Mi-Young
authors: MY
authors: Song
authors: Sang-Hwan
authors: SH
authors: Seo
authors: Su-Jin
authors: SJ
authors: Kim
authors: Bo-Gie
authors: BG
authors: Yang
authors: Myoung-Ho
authors: MH
authors: Jang
authors: Young-Chul
authors: YC
authors: Sung
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D058504:Th17 Cells / Q000276:immunology
chemical_list: D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053759:Interleukin-23; D018664:Interleukin-12; D007371:Interferon-gamma; D016264:Dextran Sulfate