Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9.
Members of the Toll-like receptor family are essential components of the innate immune system. Herein we report the molecular cloning and characterization of three novel human Toll-like receptors (hTLRs) designated hTLR7, hTLR8, and hTLR9. Human TLR7-9, like the previously described members hTLR1-6 contain an ectodomain with multiple leucine-rich repeats (LRRs) and a cytoplasmic domain homologous to that of the human interleukin-1 (IL-1) receptor. When compared with hTLR1-6, the hTLR7-9 has a higher molecular weight largely as a result of a longer ectodomain. Phylogenetic analysis shows that hTLR7-9 belong to a new sub-family of the hTLRs. Analysis of mRNA expression at the tissue levels shows differential expression patterns; hTLR7 is predominantly expressed in lung, placenta and spleen, hTLR8 is more abundant in lung, peripheral blood leukocytes, and hTLR9 is preferentially expressed in immune cell rich tissues, such as spleen, lymph node, bone marrow and peripheral blood leukocytes. The hTLR7 and hTLR8 genes are located on the sex chromosome X, hTLR9 gene is located on chromosome 3. Expression of constitutively active hTLR7-9 stimulates an NF-kappaB signaling pathway indirectly supporting the contention that these receptors are involved in cellular responses to stimuli, which activate innate immunity.
Chuang
T H
TH
Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 USA.
Ulevitch
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009928:Organ Specificity; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; C495348:TLR7 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors