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: Doo-Jin Kim, Kwang-Soon Kim, Mi-Young Song, Sang-Hwan Seo, Su-Jin Kim, Bo-Gie Yang, Myoung-Ho Jang, Young-Chul Sung
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 144 Issue 3 Pg. 190-9 (Sep 2012) ISSN: 1521-7035 [Electronic] United States
• PMID: 22836084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-12 Subunit p40
• Interleukin-17
• Interleukin-23
• Interleukin-12
• Interferon-gamma
• Dextran Sulfate

Topics

• Adenoviridae (immunology)
• Animals
• Colitis (chemically induced, immunology)
• Dextran Sulfate
• Disease Models, Animal
• Female
• Inflammation (immunology)
• Inflammatory Bowel Diseases (immunology)
• Interferon-gamma (immunology)
• Interleukin-12 (immunology)
• Interleukin-12 Subunit p40 (immunology)
• Interleukin-17 (immunology)
• Interleukin-23 (immunology)
• Intestinal Mucosa (immunology)
• Lymph Nodes (immunology)
• Mesenchymal Stem Cells (immunology)
• Mice
• Mice, Inbred C57BL
• Rats
• Rats, Sprague-Dawley
• Th17 Cells (immunology)