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{{Infobox_gene}}
{{PBB_Controls
'''Toll-like receptor 8''' is a [[protein]] that in humans is encoded by the ''TLR8'' [[gene]].<ref name="pmid11022119">{{cite journal | vauthors = Du X, Poltorak A, Wei Y, Beutler B | title = Three novel mammalian toll-like receptors: gene structure, expression, and evolution | journal = European Cytokine Network | volume = 11 | issue = 3 | pages = 362–71 | date = September 2000 | pmid = 11022119 | url = http://www.jle.com/medline.md?issn=1148-5493&vol=11&iss=3&page=362 }}</ref> TLR8 has also been designated as '''CD288''' ([[cluster of differentiation]] 288). It is a member of the [[toll-like receptor]] (TLR) family.
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Toll-like receptor 8
| HGNCid = 15632
| Symbol = TLR8
| AltSymbols =; MGC119599; MGC119600
| OMIM = 300366
| ECnumber = 
| Homologene = 44054
| MGIid = 2176887
| GeneAtlas_image1 = PBB_GE_TLR8_220832_at_tn.png
| Function = {{GNF_GO|id=GO:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0003725 |text = double-stranded RNA binding}} {{GNF_GO|id=GO:0003727 |text = single-stranded RNA binding}} {{GNF_GO|id=GO:0004888 |text = transmembrane receptor activity}} {{GNF_GO|id=GO:0005121 |text = Toll binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0007249 |text = I-kappaB kinase/NF-kappaB cascade}} {{GNF_GO|id=GO:0009597 |text = detection of virus}} {{GNF_GO|id=GO:0016064 |text = immunoglobulin mediated immune response}} {{GNF_GO|id=GO:0045078 |text = positive regulation of interferon-gamma biosynthetic process}} {{GNF_GO|id=GO:0045087 |text = innate immune response}} {{GNF_GO|id=GO:0045089 |text = positive regulation of innate immune response}} {{GNF_GO|id=GO:0045356 |text = positive regulation of interferon-alpha biosynthetic process}} {{GNF_GO|id=GO:0045359 |text = positive regulation of interferon-beta biosynthetic process}} {{GNF_GO|id=GO:0045416 |text = positive regulation of interleukin-8 biosynthetic process}} {{GNF_GO|id=GO:0051607 |text = defense response to virus}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 51311
    | Hs_Ensembl = ENSG00000101916
    | Hs_RefseqProtein = NP_057694
    | Hs_RefseqmRNA = NM_016610
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = X
    | Hs_GenLoc_start = 12834679
    | Hs_GenLoc_end = 12851205
    | Hs_Uniprot = Q9NR97
    | Mm_EntrezGene = 170744
    | Mm_Ensembl = ENSMUSG00000040522
    | Mm_RefseqmRNA = NM_133212
    | Mm_RefseqProtein = NP_573475
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = X
    | Mm_GenLoc_start = 162586799
    | Mm_GenLoc_end = 162607911
    | Mm_Uniprot = P58682
  }}
}}
'''Toll-like receptor 8''', also known as '''TLR8''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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<ref name="pmid20811154">{{cite journal | vauthors = Demaria O, Pagni PP, Traub S, de Gassart A, Branzk N, Murphy AJ, Valenzuela DM, Yancopoulos GD, Flavell RA, Alexopoulou L | title = TLR8 deficiency leads to autoimmunity in mice | journal = The Journal of Clinical Investigation | volume = 120 | issue = 10 | pages = 3651–62 | date = October 2010 | pmid = 20811154 | pmc = 2947223 | doi = 10.1172/JCI42081 }}</ref><ref name="pmid22817608">{{cite journal | vauthors = Sarvestani ST, Williams BR, Gantier MP | title = Human Toll-like receptor 8 can be cool too: implications for foreign RNA sensing | journal = Journal of Interferon & Cytokine Research | volume = 32 | issue = 8 | pages = 350–61 | date = August 2012 | pmid = 22817608 | doi = 10.1089/jir.2012.0014 }}</ref>
{{PBB_Summary
| section_title =  
| summary_text = The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which 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.<ref>{{cite web | title = Entrez Gene: TLR8 toll-like receptor 8| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51311| accessdate = }}</ref>
}}


==References==
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 [[cytokine]]s 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]]s, and lies in close proximity to another family member, [[TLR7]], on chromosome X.<ref>{{cite web |title=Entrez Gene: TLR8 toll-like receptor 8 |url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51311 |accessdate=}}</ref>
{{reflist|2}}
 
==Further reading==
TLR8 can recognize GU-rich single-stranded RNA.<ref name=pmid14976262>{{cite journal | vauthors = Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S | title = Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8 | journal = Science | volume = 303 | issue = 5663 | pages = 1526–9 | date = March 2004 | pmid = 14976262 | doi = 10.1126/science.1093620 | bibcode = 2004Sci...303.1526H }}</ref> However, the presence of GU-rich sequences in the single-stranded RNA is not sufficient to stimulate TLR8.<ref name=pmid27385120>{{cite journal | vauthors = Zhang Y, El-Far M, Dupuy FP, Abdel-Hakeem MS, He Z, Procopio FA, Shi Y, Haddad EK, Ancuta P, Sekaly RP, Said EA | title = HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses | journal = Scientific Reports | volume = 6 | pages = 29447 | date = July 2016 | pmid = 27385120 | pmc = 4935957 | doi = 10.1038/srep29447 | bibcode = 2016NatSR...629447Z }}</ref> TLR8 recognizes G-rich [[oligonucleotide]]s.<ref name="pmid16123302">{{cite journal | vauthors = Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, Wang DY, Li Y, Wang HY, Wang RF | title = Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function | journal = Science | volume = 309 | issue = 5739 | pages = 1380–4 | date = August 2005 | pmid = 16123302 | doi = 10.1126/science.1113401 | bibcode = 2005Sci...309.1380P }}</ref>
 
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.<ref name="url_invivoGen">{{cite web |url=http://www.invivogen.com/review-tlr7-tlr8 |title=TLR7 and TLR8: Key players in the antiviral response - Innate immunity |work=invivoGen  |date=Fall 2006}}</ref> TLR8 recognizes single-stranded RNA of viruses such as HIV and HCV.<ref name=pmid14976262/><ref name=pmid27385120/>
 
TLR7 is functional both in human and mouse, but TLR8 is only functional in human.<ref name=pmid22817608/>
 
==Clinical significance==
Genetic variants in TLR8 has recently been linked to susceptibility to [[pulmonary tuberculosis]].<ref name="pmid1">{{cite journal | vauthors = 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 | title = Genetic association and expression studies indicate a role of toll-like receptor 8 in pulmonary tuberculosis | journal = PLoS Genetics | volume = 4 | issue = 10 | pages = e1000218 | date = October 2008 | pmid = 18927625 | pmc = 2568981 | doi = 10.1371/journal.pgen.1000218 }}</ref>
 
===As a drug target===
TLR8 agonists (e.g. VTX-2337) have undergone clinical trials as immune stimulants in combination therapy for some cancers.<ref>[http://www.targetedonc.com/conference/sgo-2017/immune-stimulant-no-help-when-added-to-chemotherapy-for-recurrent-ovarian-cancer Immune Stimulant No Help When Added to Chemotherapy for Recurrent Ovarian Cancer. March 2017]</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Lien E, Ingalls RR | title = Toll-like receptors | journal = Critical Care Medicine | volume = 30 | issue = 1 Suppl | pages = S1-11 | date = January 2002 | pmid = 11782555 | doi = 10.1097/00003246-200201001-00001 }}
| citations =
* {{cite journal | vauthors = Kaisho T, Akira S | title = Toll-like receptors as adjuvant receptors | journal = Biochimica et Biophysica Acta | volume = 1589 | issue = 1 | pages = 1–13 | date = February 2002 | pmid = 11909637 | doi = 10.1016/S0167-4889(01)00182-3 }}
*{{cite journal | author=Lien E, Ingalls RR |title=Toll-like receptors. |journal=Crit. Care Med. |volume=30 |issue= 1 Suppl |pages= S1-11 |year= 2002 |pmid= 11782555 |doi= }}
*{{cite journal | author=Kaisho T, Akira S |title=Toll-like receptors as adjuvant receptors. |journal=Biochim. Biophys. Acta |volume=1589 |issue= 1 |pages= 1-13 |year= 2002 |pmid= 11909637 |doi= }}
}}
{{refend}}
{{refend}}


== External links ==
* {{MeshName|Toll-Like+Receptor+8}}


==External links==
{{Clusters of differentiation}}
* {{MeshName|Toll-Like+Receptor+8}}
{{TLR signaling pathway}}


{{biochem-stub}}
{{Immune receptors}}
[[Category:Toll-like receptors|8]]
[[Category:Toll-like receptors|8]]
{{protein-stub}}
[[Category:Clusters of differentiation]]


[[tr:TLR8]]
 
{{WikiDoc Sources}}
{{biochem-stub}}
{{gene-X-stub}}

Revision as of 21:57, 2 November 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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 can recognize GU-rich single-stranded RNA.[5] However, the presence of GU-rich sequences in the single-stranded RNA is not sufficient to stimulate TLR8.[6] TLR8 recognizes G-rich oligonucleotides.[7]

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.[8] TLR8 recognizes single-stranded RNA of viruses such as HIV and HCV.[5][6]

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

Clinical significance

Genetic variants in TLR8 has recently been linked to susceptibility to pulmonary tuberculosis.[9]

As a drug target

TLR8 agonists (e.g. VTX-2337) have undergone clinical trials as immune stimulants in combination therapy for some cancers.[10]

References

  1. ↑ Du X, Poltorak A, Wei Y, Beutler B (September 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 (October 2010). "TLR8 deficiency leads to autoimmunity in mice". The Journal of Clinical Investigation. 120 (10): 3651–62. doi:10.1172/JCI42081. PMC 2947223. PMID 20811154.
  3. ↑ 3.0 3.1 Sarvestani ST, Williams BR, Gantier MP (August 2012). "Human Toll-like receptor 8 can be cool too: implications for foreign RNA sensing". Journal of Interferon & Cytokine Research. 32 (8): 350–61. doi:10.1089/jir.2012.0014. PMID 22817608.
  4. ↑ "Entrez Gene: TLR8 toll-like receptor 8".
  5. ↑ 5.0 5.1 Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S (March 2004). "Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8". Science. 303 (5663): 1526–9. Bibcode:2004Sci...303.1526H. doi:10.1126/science.1093620. PMID 14976262.
  6. ↑ 6.0 6.1 Zhang Y, El-Far M, Dupuy FP, Abdel-Hakeem MS, He Z, Procopio FA, Shi Y, Haddad EK, Ancuta P, Sekaly RP, Said EA (July 2016). "HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses". Scientific Reports. 6: 29447. Bibcode:2016NatSR...629447Z. doi:10.1038/srep29447. PMC 4935957. PMID 27385120.
  7. ↑ Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, Wang DY, Li Y, Wang HY, Wang RF (August 2005). "Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function". Science. 309 (5739): 1380–4. Bibcode:2005Sci...309.1380P. doi:10.1126/science.1113401. PMID 16123302.
  8. ↑ "TLR7 and TLR8: Key players in the antiviral response - Innate immunity". invivoGen. Fall 2006.
  9. ↑ 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 (October 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.
  10. ↑ Immune Stimulant No Help When Added to Chemotherapy for Recurrent Ovarian Cancer. March 2017

Further reading

External links


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