%0 Journal Article %A Mutsumi Takigawa %A Manami Iida %A Shotaro Nagase %A Hidehiko Suzuki %A Akihiro Watari %A Minoru Tada %A Yoshiaki Okada %A Takefumi Doi %A Masayoshi Fukasawa %A Kiyohito Yagi %A Jun Kunisawa %A Masuo Kondoh %T Creation of a Claudin-2 Binder and Its Tight Junction–Modulating Activity in a Human Intestinal Model %D 2017 %R 10.1124/jpet.117.242214 %J Journal of Pharmacology and Experimental Therapeutics %P 444-451 %V 363 %N 3 %X Disruption of the gastrointestinal epithelial barrier is a hallmark of chronic inflammatory bowel diseases (IBDs). The transmembrane protein claudin 2 (CLDN2) is a component of epithelial tight junctions (TJs). In the intestines of patients with IBDs, the expression of the pore-forming TJ protein CLDN2 is upregulated. Although CLDN2 is involved in these leaky barriers, whether it can be a target to enhance TJ integrity is unknown because a CLDN2-specific inhibitor has not been developed. Here, we used DNA immunization to generate a monoclonal antibody (mAb) that recognized an extracellular loop of CLDN2. Treatment of epithelial cell monolayers with the mAb increased barrier integrity. In addition, the anti-CLDN2 mAb attenuated the decrease in TJ integrity induced by the proinflammatory cytokine tumor necrosis factor-α (TNF-α), and cotreatment of cells with anti–TNF-α mAb and anti-CLDN2 mAb showed additive attenuating effects. These findings indicate that CLDN2 may be a target for enhancing TJ integrity, and CLDN2 binder may be an enhancer of mucosal barrier integrity and a potential therapeutic option for IBDs. %U https://jpet.aspetjournals.org/content/jpet/363/3/444.full.pdf