Identification and expression profiling of a human C-type lectin, structurally homologous to mouse dectin-2.
A number of C-type lectins on antigen-presenting cells play an important role in regulating innate immunity. Previously, we identified the mouse C-type lectins (dectin-1, and dectin-2) and human DECTIN-1. To identify human DECTIN-2, we employed degenerative polymerase chain reaction-based cDNA cloning using RNA from human Langerhans cell (LC)-like dendritic cells (DCs). This process yielded a cDNA encoding a C-type lectin with 66.5% amino acid sequence homology to mouse dectin-2, the same gene reported by Kanazawa et al. (J Invest Dermatol 2004: 122: 1522-1524) using the disparate approach of analyzing coding sequences in chromosome 12. Similar to their findings, we found gene expression in lung, spleen, and lymph node. Among resting leukocytes, it was expressed at highest levels by CD14+ monocytes, at lower levels by CD19+ B cells, and not at all by CD4+ T cells. Activation of CD19+ B cells with pokeweed mitogen down-regulated gene expression, whereas expression in CD4+ T cells was induced by Con A. Among our novel findings are an alternatively spliced transcript lacking exon 2, expression in bone marrow and tonsil, expression in CD8+ T cells that is abrogated following activation with phytohemagglutinin, restricted expression to CD1a+ LC within epidermis, and preferential expression by plasmacytoid (rather than myeloid) DC. Finally, we found that treatment with interleukin-4 (IL-4), IL-10, or UVB down regulated gene expression in CD14+ monocytes, whereas granulocyte-macrophage colony-stimulating factor, transforming growth factor-beta1, or tumor necrosis factor-alpha treatment up-regulated it. Our findings may form the basis for understanding the function of human DECTIN-2 in innate immunity.
Gavino
Alde Carlo P
AC
Department of Dermatology, The University of Texas South Western Medical Center and Dermatology Section (Medical Service), Dallas Veterans Affairs Medical Center, Dallas, TX 75390-9069, USA.
Chung
Jin-Sung
JS
Sato
Kota
K
Ariizumi
Kiyoshi
K
Cruz
Ponciano D
PD
D000595:Amino Acid Sequence; D000818:Animals; D018949:Antigens, CD1 / Q000096:biosynthesis; D015139:Blotting, Southern; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D015536:Down-Regulation; D005091:Exons; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000737:chemistry*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008934:Mitogens; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000378:metabolism; D011487:Protein Conformation; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014466:Ultraviolet Rays; D015854:Up-Regulation
D018949:Antigens, CD1; C419393:CD1a antigen; D018076:DNA, Complementary; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D008934:Mitogens; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C445340:dectin-2, mouse; D012313:RNA