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 in nate immune system, Herein we report the molecular cloning and characteriza tion of three novel human Toll-like receptors (hTLRs) designated hTLR7, hTL R8, and hTLR9, Human TLR7-9, like the previously described members hTLR1-6 contain an ectodomain with multiple leucine-rich repeats (LRRs) and a cytop lasmic 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 lar gely as a result of a longer ectodomain. Phylogenetic analysis shows that h TLR7-9 belong to a new sub-family of the hTLRs, Analysis of mRNA expression at the tissue levels shows differential expression patterns; hTLR7 is pred ominantly expressed in lung, placenta and spleen, hTLR8 is more abundant in lung, peripheral blood leukocytes, and hTLR9 is preferentially expressed i n immune cell rich tissues, such as spleen, lymph node, bone marrow and per ipheral blood leukocytes. The hTLR7 and hTLR8 genes are located on the sex chromosome X, hTLR9 gene is located on chromosome 3, Expression of constitu tively active hTLR7-9 stimulates an NF-kappaB signaling pathway indirectly supporting the contention that these receptors are involved in cellular res ponses to stimuli, which activate innate immunity.