Identification and expression of mouse Langerin (CD207) in dendritic cells.
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)-beta1. Unexpectedly, significant amounts of m-Langerin transcripts were detected in skin and LN of TGF-beta1-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-beta1, DC subsets, DC maturation and the tissue environment.
Takahara
Kazuhiko
K
Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, 606-8502, Japan.
Omatsu
Yoshiki
Y
Yashima
Yusuke
Y
Maeda
Yasuhiro
Y
Tanaka
Shusaku
S
Iyoda
Tomonori
T
Clausen
Björn E
BE
Matsubara
Kazumi
K
Letterio
John
J
Steinman
Ralph M
RM
Matsuda
Yoichi
Y
Inaba
Kayo
K
Clusen
Bjöern
B
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D001854:Bone Marrow Cells / Q000378:metabolism; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003713:Dendritic Cells / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D008351:Mannans / Q000378:metabolism; D037241:Mannose-Binding Lectins; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008957:Models, Genetic; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D015703:Antigens, CD; D000954:Antigens, Surface; C121916:CD207 protein, human; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D008351:Mannans; D037241:Mannose-Binding Lectins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1