Toll-like receptor 8 is a
protein that in humans is encoded by the ''TLR8''
gene.
TLR8 has also been designated as CD288 (
cluster of differentiation 288). It is a member of the
toll-like receptor (TLR) family.
Function
TLR8 seems to function differently in humans and mice. Until recently, TLR8 was believed to be nonfunctional in mice, but it seems to counteract TLR7 activity
The TLR family plays a fundamental role in pathogen recognition and activation of
innate immunity. TLRs are highly conserved from ''
Drosophila'' 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
cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is predominantly expressed in lung and peripheral blood
leukocyte
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
s, and lies in close proximity to another family member,
TLR7
Toll-like receptor 7, also known as TLR7, is a protein that in humans is encoded by the ''TLR7'' gene. Orthologs are found in mammals and birds. It is a member of the toll-like receptor (TLR) family and detects single stranded RNA.
Function ...
, on chromosome X. Recent research has also shown the expression of TLR8 in hippocampal interneurons, with yet unknown function.
TLR8 can recognize GU-rich single-stranded RNA.
However, the presence of GU-rich sequences in the single-stranded RNA is not sufficient to stimulate TLR8.
TLR8 recognizes G-rich
oligonucleotides.
TLR8 is an endosomal receptor that recognizes single stranded RNA (ssRNA), and can recognize ssRNA viruses such as Influenza, Sendai, and Coxsackie B viruses. TLR8 binding to the viral RNA recruits MyD88 and leads to activation of the transcription factor NF-κB and an antiviral response.
TLR8 recognizes single-stranded RNA of viruses such as HIV and HCV.
[
]
Clinical significance
Genetic variants in TLR8 has recently been linked to susceptibility to pulmonary tuberculosis.
As a drug target
* TLR8 agonists (e.g. VTX-2337) have undergone clinical trials as immune stimulants in combination therapy for some cancers.Immune Stimulant No Help When Added to Chemotherapy for Recurrent Ovarian Cancer. March 2017
/ref>
* TLR8 antagonists (e.g. CU-CPT9a) may have therapeutic applications against autoimmune disorders.
References
Further reading
*
*
External links
*
PDBe-KB
provides an overview of all the structure information available in the PDB for Human Toll-like receptor 8 (TLR8)
8
Clusters of differentiation
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