Intraepithelial lymphocytes express junctional molecules in murine small intestine Kyoko Inagaki-Ohara a, * , Akira Sawaguchi b , Tatsuo Suganuma b , Goro Matsuzaki c , Yukifumi Nawa a a Parasitic Diseases Unit, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan b Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan c Molecular Microbiology Group, Center of Molecular Biosciences, University of the Ryukyus, Senbaru, Nishihara, Okinawa 903-0213, Japan Received 1 April 2005 Available online 13 April 2005 Abstract Intestinal intraepithelial lymphocytes (IEL) that reside at basolateral site regulate the proliferation and differentiation of epithe- lial cells (EC) for providing a first line of host defense in intestine. However, it remains unknown how IEL interact and communicate with EC. Here, we show that IEL express junctional molecules like EC. We identified mRNA expression of the junctional molecules in IEL such as zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM) (tight junction), b-catenin and E-cad- herin (adherens junction), and connexin26 (gap junction). IEL constitutively expressed occludin and E-cadherin at protein level, while other T cells in the thymus, spleen, liver, mesenteric lymph node, and PeyerÕs patches did not. cd IEL showed higher level of these expressions than ab IEL. The expression of occludin was augmented by anti-CD3 Ab stimulation. These results suggest the possibility of a novel role of IEL concerning epithelial barrier and communication between IEL and EC. Ó 2005 Elsevier Inc. All rights reserved. Keywords: Small intestine; Intestinal intraepithelial lymphocytes; Epithelial cells; Junctional molecules The intestinal epithelium has evolved structurally to form a barrier between the antigen-rich environment of the lumen and the sterile internal environment of the organism. A single-cell layer of epithelial cells joined firmly together by tight junctions forms a continuous impermeable belt to prevent paracellular crossing of luminal contents [1,2]. To maintain homeostasis and preserve the integrity of the epithelial barrier, the inter- cellular junctional complex that consists of tight junc- tions, adherens junctions, desmosomes, and gap junctions is thought to facilitate appropriate cell–cell interaction between epithelial cells (EC). Although intraepithelial lymphocytes (IEL) exist between EC and contribute to construct epithelial barrier, previous investigations on junctional proteins have been focused on interaction between EC. Thus, only little information is available concerning the physical interaction between EC and IEL. IEL participate in immune surveillance and regula- tion of the intestinal immune system [3–5]. Murine IEL comprise an approximately equal frequency of pop- ulation bearing T-cell receptor (TCR) ab and TCR cd [6]. cd IEL are considered to be a T-cell population play- ing an important role in the first line of host defense against a variety of antigens and pathogens [7,8]. Intes- tinal cd T cells have been reported to play an important role for the maintenance of homeostasis in intestine, by regulating the generation and differentiation of EC [9]. Recently, we have found the protective role of cd IEL against colitis as regulatory T cells in cooperation with 0006-291X/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2005.04.025 * Corresponding author. Fax: +81 985 84 3887. E-mail address: INAGAKI@med.miyazaki-u.ac.jp (K. Inagaki- Ohara). www.elsevier.com/locate/ybbrc Biochemical and Biophysical Research Communications 331 (2005) 977–983 BBRC