Toll-like receptor 10 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''TLR10''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
TLR10 has also been designated as CD290 (
cluster of differentiation 290).
TLR10 has not been extensively studied because it is a pseudogene in mice, though all other mammalian species contain an intact copy of the TLR10 gene. Unlike other TLRs, TLR10 does not activate the immune system and has instead been shown to suppress inflammatory signaling on primary human cells. This makes TLR10 unique among the TLR family. TLR10 was thought to be an "orphan" receptor, however, recent studies have identified ligands for TLR10 and these include HIV-gp41. Ligands for TLR2 are potential ligands for TLR10.
Function
The protein encoded by this gene is a member of the
toll-like receptor
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize ...
(TLR) family which play a fundamental role in pathogen recognition and activation of
innate immunity. TLRs are highly conserved from ''
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...
'' to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
s necessary for the development of effective immunity.
TLR10 is unique among the TLR family in having an anti-inflammatory function, rather than a pro-inflammatory function. This was discovered by over-expressing TLR10 in human cell lines and using antibody-mediated engagement of the receptor on primary human cells. When TLR10 is activated in this manner, it suppresses the amount of cytokines produced, as compared to control cells. TLR10 engagement also has long-term effects on monocyte and B cell activation/differentiation by suppressing the transcription of activation markers. TLR10's mechanism of action is not yet known but activation of the receptor has been shown to suppress NF-κB, MAP kinase and Akt signaling events stimulated by TLR and CD40 ligands. Currently, no ligand has been identified for this receptor. However, the computational analysis reported that TLR10 can interact with peptidoglycan and (triacyl) lipopeptides in concert with TLR2 (as a heterodimer).
Some ligands of TLR10 have been recently described: HIV-1 gp41, ''H. pylori'' LPS (TLR2/10), ''L. monocytogenes, B burgdorferi,'' H1N1/H5N1.
Expression
TLR10 has been transcriptionally shown to be expressed in secondary lymphoid tissues such as the spleen, lymph nodes, and tonsils. More specifically, protein level expression of TLR10 has been shown on the surface of B cells, monocytes and neutrophils; but not on T cells. Monocytes have the highest expression of TLR10 among these cell types but the overall expression of TLR10 is low compared to other TLRs. TLR10 has also been shown to be produced intracellularly in neutrophils and B cells differentiating into plasma cells.
Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.
References
Further reading
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External links
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Clusters of differentiation
10
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