Tissue & Cell 36 (2004) 121–127 Expression of cys–cys chemokine ligand 21 on human gingival lymphatic vessels Shin-ichiro Kuroshima a,∗ , Yoshihiko Sawa b , Yuji Yamaoka b , Kenji Notani a , Shigemitsu Yoshida b , Nobuo Inoue a a Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University, N13 W7, Kita-ku, Sapporo 060-8586, Japan b Department of Oral Functional Science, Graduate School of Dental Medicine, Hokkaido University, N13 W7, Kita-ku, Sapporo 060-8586, Japan Received 1 September 2003; accepted 28 October 2003 Abstract The cys–cys (C–C) chemokine ligand 21 is a member of the C–C chemokines that constitute a group of heparin-binding cytokines with a pattern of four or six conserved cysteines. The CCL21 is known to be expressed in secondary lymphoid tissues, however it has rarely been reported for the expression on peripheral lymphatic vessels in somatic tissue. Here we investigated the expression of CCL21 on lymphatic vessels identified by anti-desmoplakin in uninflamed and inflamed human gingiva. In uninflamed tissue the expression of CCL21 was detected on lymphatic vessels in gingiva. In uninflamed gingiva the expression of CCL21 was detected on all lymphatic capillaries of the mucosal connective tissue papillae. There were two types of collecting lymphatic vessels in the lamina propria mucosae expressing CCL21 strongly or very weakly. In inflamed gingiva no expression of CCL21 was detected on lymphatic vessels. In all tissue sections no blood vessels expressing CCL21 were observed. These results may suggest that the expression of CCL21 is predominantly induced in the peripheral lymphatic endothelium of the uninflamed mucosal microcirculation, and that under inflamed conditions a reduction of CCL21 occurs in lymphatic endothelium. © 2003 Elsevier Ltd. All rights reserved. Keywords: Desmoplakin; CCL21; Lymphatic endothelium; Human gingiva 1. Introduction The cys–cys (C–C) chemokine ligand 21 (CCL21)/ secondary lymphoid-tissue chemokine is a C–C chemokine, a group of small, mostly basic, heparin-binding cytokines with common structural features that exhibit a pattern of four or six conserved cysteines (Nagira et al., 1997). The CCL21 is expressed on the high endothelial venules and lymphatic vessels of lymph nodes and Peyer’s patches (Gunn et al., 1998). The CCL21 is a highly efficacious chemoattractant for lymphocytes and mature dendritic cells expressing its receptor, C–C chemokine receptor 7 (CCR7), which is the major homing receptor directing them into secondary lymphoid organs (Gunn et al., 1999; Saeki et al., 1999). In the periphery of the mucosa immature Langerhans cells and dendritic cells capture intruder antigens and start ∗ Corresponding author. Tel.: +81-11-706-4219; fax: +81-11-706-4928. E-mail address: sk@den.hokudai.ac.jp (S.-i. Kuroshima). the maturation process which leads to the CCR7 expression (Caux et al., 2002; Cirrincione et al., 2002). It is thought that there are microcirculation systems which produce CCL21 and allow mature immunocytes expressing CCR7 to home in from the periphery of the mucosa to secondary lymphoid tissue. The identification of lymphatic vessels were performed by monoclonal antibodies for desmoplakin and platelet- endothelial cell adhesion molecule-1 (PECAM-1). It has been revealed that lymphatic but not blood endothelium expresses desmoplakin in human small intestine and tongue by immuno-electron microscopic studies, and it is known that lymphatic vessels also express PECAM-1 (Ebata et al., 2001a,b). Desmoplakin is a desmosome-associated protein found in epithelia, and lymphatic vessels were iden- tified by anti-desmoplakin after the discrimination from the gingival epithelia by anti-PECAM-1. This study aims to in- vestigate the expression of CCL21 on peripheral lymphatic endothelium in mucosal microcirculation under inflamed and uninflamed conditions. 0040-8166/$ – see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.tice.2003.10.004