Immunobiology 213 (2008) 715–728 The lymph vessel network in mouse skin visualised with antibodies against the hyaluronan receptor LYVE-1 Christoph H. Tripp a , Bernhard Haid a , Vincent Flacher a , Michael Sixt b , Hannes Peter c , Julia Farkas c , Robert Gschwentner d , Lydia Sorokin e , Nikolaus Romani a , Patrizia Stoitzner a,Ã a Department of Dermatology and Venereology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria b Max-Planck-Institute for Biochemistry, Martinsried, Germany c Department of Microbiology, University of Innsbruck, Innsbruck, Austria d Department of Zoology, University of Innsbruck, Innsbruck, Austria e Institute for Physiological Chemistry and Pathobiochemistry, Mu¨nster University, Germany Received 23 July 2008; accepted 23 July 2008 Abstract Langerhans cells and dermal dendritic cells migrate to the draining lymph nodes through dermal lymphatic vessels. They do so in the steady-state and under inflammatory conditions. Peripheral T cell tolerance or T cell priming, respectively, are the consequences of migration. The nature of dendritic cell-containing vessels was mostly defined by electron microscopy or by their lack of blood endothelial markers. Selective markers for murine lymph endothelium were hitherto rare or not available. Here, we utilised recently developed antibodies against the murine hyaluronan receptor, LYVE-1, to study the lymph vessel network in mouse skin in more detail. In hairless skin from the ears, lymph vessels were spread out in a horizontal plane. They formed anastomoses, and they possessed frequent blind endings that were occasionally open. Lymph vessels were wider than blood vessels, which were identified by their strong CD31 expression. In body wall skin LYVE-1 reactive vessels did not extend laterally but they dived straight down into the deeper dermis. There, they are connected to each other and formed a network similar to ear skin. The number and width of lymph vessels did not grossly change upon inflammatory stimuli such as skin explant culture or tape stripping. There were also no marked changes in caliber in response to the TLR 7/8 ligand Imiquimod. Double-labelling experiments of cultured skin showed that most of the strongly cell surface MHC II-expressing (i.e. activated) dendritic cells were confined to the lymph vessels. Langerin/CD207 + cells within this population appeared later than dermal dendritic cells, i.e. langerin-negative cells. Comparable results were obtained after stimulating the skin in vivo with the TLR 7/8 ligand Imiquimod or by tape stripping. In untreated skin (i.e. steady state) a few MHC II + and Langerin/CD207 + cells, presumably migrating skin dendritic cells including epidermal Langerhans cells, were consistently observed within the lymph vessels. The novel ARTICLE IN PRESS www.elsevier.de/imbio 0171-2985/$ - see front matter r 2008 Elsevier GmbH. All rights reserved. doi:10.1016/j.imbio.2008.07.025 Abbreviation: TLR, toll-like receptor. Ã Corresponding author. E-mail address: patrizia.stoitzner@i-med.ac.at (P. Stoitzner).