TLR8

Toll-like receptor 8
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3W3G​, 3W3J​, 3W3K​, 3W3L​, 3W3M​, 3W3N​, 3WN4​, 4QBZ​, 4QC0​, 4R07​, 4R08​, 4R09​, 4R0A​
Identifiers
Symbols	TLR8 ; CD288
External IDs	OMIM: 300366 MGI: 2176887 HomoloGene: 44054 ChEMBL: 5805 GeneCards: TLR8 Gene
Gene ontology Molecular function • DNA binding • RNA binding • double-stranded RNA binding • single-stranded RNA binding • receptor activity • drug binding Cellular component • Golgi membrane • endoplasmic reticulum membrane • endosome membrane • integral component of membrane • endolysosome membrane Biological process • microglial cell activation • regulation of protein phosphorylation • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • inflammatory response • I-kappaB kinase/NF-kappaB signaling • response to virus • immunoglobulin mediated immune response • toll-like receptor 8 signaling pathway • toll-like receptor 9 signaling pathway • positive regulation of interferon-gamma biosynthetic process • innate immune response • positive regulation of innate immune response • positive regulation of interferon-alpha biosynthetic process • positive regulation of interferon-beta biosynthetic process • positive regulation of interleukin-8 biosynthetic process • regulation of cytokine secretion • defense response to virus • cellular response to mechanical stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	51311	170744
Ensembl	ENSG00000101916	ENSMUSG00000040522
UniProt	Q9NR97	P58682
RefSeq (mRNA)	NM_016610	NM_133212
RefSeq (protein)	NP_057694	NP_573475
Location (UCSC)	Chr X: 12.91 – 12.92 Mb	Chr X: 167.24 – 167.26 Mb
PubMed search

Toll-like receptor 8 is a protein that in humans is encoded by the TLR8 gene.^[1] 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^[2][3]

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 leukocytes, and lies in close proximity to another family member, TLR7, on chromosome X.^[4]

TLR8 recognizes G-rich oligonucleotides.^[5]

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-kB and an antiviral response.^[6]

Clinical significance

Genetic variants in TLR8 has recently been linked to susceptibility to pulmonary tuberculosis.^[7]

TLR7 is functional both in human and mouse, but TLR8 is only functional in human.^[3]

References

1. Du X, Poltorak A, Wei Y, Beutler B (Sep 2000). "Three novel mammalian toll-like receptors: gene structure, expression, and evolution". European Cytokine Network 11 (3): 362–71. PMID 11022119.
2. Demaria O, Pagni PP, Traub S, de Gassart A, Branzk N, Murphy AJ, Valenzuela DM, Yancopoulos GD, Flavell RA, Alexopoulou L (2010). "TLR8 deficiency leads to autoimmunity in mice". J. Clin. Invest. 120 (10): 3651–62. doi:10.1172/JCI42081. PMC 2947223. PMID 20811154.
3. Sarvestani ST, Williams BR, Gantier MP (Aug 2012). "Human Toll-like receptor 8 can be cool too: implications for foreign RNA sensing". Journal of Interferon & Cytokine Research: The Official Journal of the International Society for Interferon and Cytokine Research 32 (8): 350–61. doi:10.1089/jir.2012.0014. PMID 22817608.
4. "Entrez Gene: TLR8 toll-like receptor 8".
5. Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, Wang DY, Li Y, Wang HY, Wang RF (Aug 2005). "Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function". Science 309 (5739): 1380–4. doi:10.1126/science.1113401. PMID 16123302.
6. "TLR7 and TLR8: Key players in the antiviral response - Innate immunity". invivoGen. Fall 2006.
7. Davila S, Hibberd ML, Hari Dass R, Wong HE, Sahiratmadja E, Bonnard C, Alisjahbana B, Szeszko JS, Balabanova Y, Drobniewski F, van Crevel R, van de Vosse E, Nejentsev S, Ottenhoff TH, Seielstad M (Oct 2008). "Genetic association and expression studies indicate a role of toll-like receptor 8 in pulmonary tuberculosis". PLoS Genetics 4 (10): e1000218. doi:10.1371/journal.pgen.1000218. PMC 2568981. PMID 18927625.

Further reading

• Lien E, Ingalls RR (Jan 2002). "Toll-like receptors". Critical Care Medicine 30 (1 Suppl): S1–11. doi:10.1097/00003246-200201001-00001. PMID 11782555.
• Kaisho T, Akira S (Feb 2002). "Toll-like receptors as adjuvant receptors". Biochimica et Biophysica Acta 1589 (1): 1–13. doi:10.1016/S0167-4889(01)00182-3. PMID 11909637.

External links

• Toll-Like Receptor 8 at the US National Library of Medicine Medical Subject Headings (MeSH)