TY - JOUR T1 - Creation of a Claudin-2 Binder and Its Tight Junction–Modulating Activity in a Human Intestinal Model JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 444 LP - 451 DO - 10.1124/jpet.117.242214 VL - 363 IS - 3 AU - Mutsumi Takigawa AU - Manami Iida AU - Shotaro Nagase AU - Hidehiko Suzuki AU - Akihiro Watari AU - Minoru Tada AU - Yoshiaki Okada AU - Takefumi Doi AU - Masayoshi Fukasawa AU - Kiyohito Yagi AU - Jun Kunisawa AU - Masuo Kondoh Y1 - 2017/12/01 UR - http://jpet.aspetjournals.org/content/363/3/444.abstract N2 - 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. ER -