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
The TLR family plays an important 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
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
,
placenta, and
spleen, and lies in close proximity to another family member,
TLR8
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 d ...
, on the human X chromosome.
TLR7 recognizes single-stranded
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
in
endosomes, which is a common feature of
viral
Viral means "relating to viruses" (small infectious agents).
Viral may also refer to:
Viral behavior, or virality
Memetic behavior likened that of a virus, for example:
* Viral marketing, the use of existing social networks to spread a marke ...
genomes which are internalised by
macrophages and
dendritic cell
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...
s. TLR7 recognizes single-stranded RNA of viruses such as
HIV
The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...
and
HCV.
TLR7 can recognize GU-rich single-stranded RNA.
[ However, the presence of GU-rich sequences in the single-stranded RNA is not sufficient to stimulate TLR7.][
]
Clinical significance
TLR7 has been shown to play a significant role in the pathogenesis of autoimmune disorders such as lupus
Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
as well as in the regulation of antiviral immunity. Although not yet fully elucidated, using an unbiased genome-scale screen with short hairpin RNA (shRNA), it has been demonstrated that the receptor TREML4 acts as an essential positive regulator of TLR7 signaling. In TREML4 -/- mice macrophages that are hyporesponsive to TLR7 agonists, macrophages fail to produce type I interferons due to impaired phosphorylation of the transcription factor STAT1 by the mitogen-activated protein kinase p38
p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell different ...
and decreased recruitment of the adaptor MYD88 to TLR7. TREML4 deficiency reduced the production of inflammatory cytokines and autoantibodies in MRL/lpr mice, suggesting that TLR7 is a vital component of antiviral immunity and a predecessor factor in the pathogenesis of rheumatic diseases such as systemic lupus erythematosus
Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
(SLE).beta-cyclodextrin
Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzymatic conversion. They are used in food, pharmaceutica ...
.
In July 2020, it was discovered that a deficient TLR7 gene caused several young patients to become seriously ill after being infected by SARS-CoV-2.
Type I Interferon Induction and Signaling During SARS-CoV-2 Infection
o
WikiPathways
References
Further reading
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External links
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