TLR9- cluster of differentiation 289

Toll-like receptor 9 (TLR9) often known as CD289 (cluster of differentiation 289), is a member of the Toll-like receptor family that recognizes pathogen-associated molecular pattern. TLR9 was first cloned and identified as a receptor for unmethylated CpG-DNA as well as for bacterial DNA. It is essential not only for pro-inflammatory cytokine production and other inflammatory responses, but it also plays a role in the induction of T helper 1 (Th1) acquired immune response and in the proliferation of B cells. Like all other members of the TLR family, TLR9 is composed of an extracellular domain containing multiple leucine-rich repeats (LRRs), a transmembrane region, and a cytoplasmic tail containing the conserved TIR domain. The TLR9 sequence encodes a 1032 aa protein containing 27 N-terminal LRRs with a calculated molecular weight of 116 kDa . The gene for TLR9 has been mapped to human chromosome 3p21.3. TLR9 is most closely related to TLR7 and TLR8 with 36% and 35% overall amino acid sequence identity, respectively and thus along with TLR7 and TLR8 constitutes a new sub-family of the TLRs.

In vivo, TLR9 mRNA is expressed in spleen, lymph node, bone marrow, and PBLs. (1) Specifically, TLR9 mRNA is expressed at the highest levels in B cells and dendritic cells (DC). In vitro, TLR9 is moderately upregulated by autocrine IFN-γ, IL-1ß, IL-6, IL-10, and TNF-α in PMA-differentiated THP-1 cells. TLR9 mRNA expression in THP-1 cells is unaffected by exposure to both Gram-positive and Gram-negative bacteria. Ex vivo, TLR9 expression in monocytes and particularly in granulocytes is downregulated in response to Gram-negative bacteria. (2, 3) TLR9 also appears to be localized internally, perhaps in lysosomic or endocytic compartments where it would more likely encounter PAMPs including unmethylated DNA.

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