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International Immunology, Vol. 14, No. 5, pp. 433-444, May 2002
© 2002 Japanese Society for Immunology

Identification and expression of mouse Langerin (CD207) in dendritic cells

Kazuhiko Takahara1, Yoshiki Omatsu1, Yusuke Yashima1, Yasuhiro Maeda1, Shusaku Tanaka1, Tomonori Iyoda2, Bjöern Clusen5, Kazumi Matsubara3, John Letterio6, Ralph M. Steinman7, Yoichi Matsuda4 and Kayo Inaba1

1 Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, and 2 Department of Zoology, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan 3 Laboratory of Cytogenetics, Division of Bioscience, Graduate School of Environmental Earth Science and 4 Chromosome Research Unit, Faculty of Science, Hokkaido University, Hokkaido 060-08IO, Japan 5 Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105AZ Amsterdam, The Netherlands 6 National Cancer Institute, NIH, Bethesda, MD 20892-5055, USA 7 Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021-6399, USA

Correspondence to: K. Inaba; E-mail: kayo{at}lif.kyoto-u.ac.jp
Transmitting editor: T. Hirano

We have cloned the mouse homologue of human Langerin (h-Langerin), a type II transmembrane protein with a single external C-type lectin domain. Mouse Langerin (m-Langerin) displays 65 and 74% homologies in total amino acid and lectin domains with those of h-Langerin. The cognate mouse and rat genes were assigned to chromosome 6D1–D2 and chromosome 4q33 distal–q34.1 proximal respectively, syntenic to the h-Langerin gene on chromosome 2p13. With RT-PCR, m-Langerin transcripts were as expected detected in MHC class II+, but not MHC class II–, cells from epidermis and the expression level was reduced by culture. However, m-Langerin transcripts were also expressed in spleen, lymph nodes (LN), thymus, liver, lung and even heart, but not gut-associated lymphoid tissues. In single-cell lymphoid suspensions, m-Langerin transcripts were mainly detected in the CD11c+ dendritic cells (DC), especially the CD11blow/CD8high fraction of spleen and LN. DC generated from bone marrow precursors by granulocyte macrophage colony stimulating factor (GM-CSF) expressed m-Langerin, but this was shut down during maturation with CD40 ligand or lipopolysaccharide. DC derived from blood monocytes by GM-CSF + IL-4 lacked m-Langerin unless the cultures were supplemented with transforming growth factor (TGF)-ß1. Unexpectedly, significant amounts of m-Langerin transcripts were detected in skin and LN of TGF-ß1-deficient mice, although in much lower amounts than littermate controls. Recombinant m-Langerin could form multimers and bind to mannan–agarose. These findings indicate that Langerin expression is regulated at several levels: by TGF-ß1, DC subsets, DC maturation and the tissue environment.

Keywords: Birbeck granules, C-type lectin, gene mapping, Langerhans cells, multimer, transforming growth factor-ß1


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