Toll-like receptor 10 is a protein that in humans is encoded by the TLR10gene.[3] 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.[4] 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.[5] Ligands for TLR2 are potential ligands for TLR10.[6]
The protein encoded by this gene is a member of the toll-like receptor (TLR) family which play 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.
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.[7] 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).[8]
Some ligands of TLR10 have been recently described: HIV-1 gp41, H. pylori LPS (TLR2/10), L. monocytogenes, B burgdorferi, H1N1/H5N1.[9]
ExpressionEdit
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.[10]
ReferencesEdit
^ abcGRCh38: Ensembl release 89: ENSG00000174123 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Chuang T, Ulevitch RJ (Mar 2001). "Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells". Biochim Biophys Acta. 1518 (1–2): 157–61. doi:10.1016/s0167-4781(00)00289-x. PMID 11267672.
^Jiang S, Li X, Hess NJ, Guan Y, Tapping RI (May 2016). "TLR10 is a Negative Regulator of Both MyD88-Dependent and -Independent TLR Signaling". Journal of Immunology. 196 (9): 3834–3841. doi:10.4049/jimmunol.1502599. PMC4868647. PMID 27022193.
^Fore, Faith; Indriputri, Cut; Mamutse, Janet; Nugraha, Jusak (2020). "TLR10 and Its Unique Anti-Inflammatory Properties and Potential Use as a Target in Therapeutics". Immune Network. 20 (3): e21. doi:10.4110/in.2020.20.e21. ISSN 1598-2629. PMC7327153. PMID 32655969.
^Su, Si‐Biao; Tao, Lin; Deng, Ze‐Ping; Chen, Wen; Qin, Shan‐Yu; Jiang, Hai‐Xing (April 2021). "TLR10: Insights, controversies and potential utility as a therapeutic target". Scandinavian Journal of Immunology. 93 (4): e12988. doi:10.1111/sji.12988. ISSN 0300-9475. PMID 33047375.
^Hess NJ, Jiang S, Li X, Guan Y, Tapping RI (Jan 2017). "TLR10 Is a B Cell Intrinsic Suppressor of Adaptive Immune Responses". Journal of Immunology. 198 (2): 699–707. doi:10.4049/jimmunol.1601335. PMC5225023. PMID 27956526.
^Govindaraj RG, Manavalan B, Lee G, Choi S (September 2010). "Molecular Modeling-Based Evaluation of hTLR10 and Identification of Potential Ligands in Toll-Like Receptor Signaling". PLOS ONE. 5 (9): e12713. Bibcode:2010PLoSO...512713G. doi:10.1371/journal.pone.0012713. PMC2943521. PMID 20877634.
^Sartorius R, Trovato M, Manco R, D'Apice L, De Berardinis P (October 2021). "Exploiting viral sensing mediated by Toll-like receptors to design innovative vaccines". npj Vaccines. 6 (1): 127. doi:10.1038/s41541-021-00391-8. PMC8553822. PMID 34711839.
toll, like, receptor, protein, that, humans, encoded, tlr10, gene, tlr10, also, been, designated, cd290, cluster, differentiation, tlr10, been, extensively, studied, because, pseudogene, mice, though, other, mammalian, species, contain, intact, copy, tlr10, ge. Toll like receptor 10 is a protein that in humans is encoded by the TLR10 gene 3 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 4 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 5 Ligands for TLR2 are potential ligands for TLR10 6 TLR10Available structuresPDBHuman UniProt search PDBe RCSBList of PDB id codes2J67IdentifiersAliasesTLR10 CD290 toll like receptor 10External IDsOMIM 606270 HomoloGene 12809 GeneCards TLR10Gene location Human Chr Chromosome 4 human 1 Band4p14Start38 772 238 bp 1 End38 782 990 bp 1 RNA expression patternBgeeHumanMouse ortholog Top expressed inlymph nodeappendixspleenbloodmonocytethymusbone marrow cellssuperficial temporal arteryrectumgallbladdern aMore reference expression dataBioGPSn aGene ontologyMolecular functiontransmembrane signaling receptor activity protein binding identical protein bindingCellular componentintegral component of membrane plasma membrane membrane integral component of plasma membraneBiological processtoll like receptor 10 signaling pathway inflammatory response positive regulation of inflammatory response MyD88 dependent toll like receptor signaling pathway signal transduction immune system process innate immune response toll like receptor signaling pathway immune responseSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez81793n aEnsemblENSG00000174123n aUniProtQ9BXR5n aRefSeq mRNA NM 001017388NM 001195106NM 001195107NM 001195108NM 030956n aRefSeq protein NP 001017388NP 001182035NP 001182036NP 001182037NP 112218n aLocation UCSC Chr 4 38 77 38 78 Mbn aPubMed search 2 n aWikidataView Edit Human Contents 1 Function 2 Expression 3 References 4 Further reading 5 External linksFunction EditThe protein encoded by this gene is a member of the toll like receptor TLR family which play 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 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 kB MAP kinase and Akt signaling events stimulated by TLR and CD40 ligands 7 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 8 Some ligands of TLR10 have been recently described HIV 1 gp41 H pylori LPS TLR2 10 L monocytogenes B burgdorferi H1N1 H5N1 9 Expression EditTLR10 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 10 References Edit a b c GRCh38 Ensembl release 89 ENSG00000174123 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Chuang T Ulevitch RJ Mar 2001 Identification of hTLR10 a novel human Toll like receptor preferentially expressed in immune cells Biochim Biophys Acta 1518 1 2 157 61 doi 10 1016 s0167 4781 00 00289 x PMID 11267672 Jiang S Li X Hess NJ Guan Y Tapping RI May 2016 TLR10 is a Negative Regulator of Both MyD88 Dependent and Independent TLR Signaling Journal of Immunology 196 9 3834 3841 doi 10 4049 jimmunol 1502599 PMC 4868647 PMID 27022193 Fore Faith Indriputri Cut Mamutse Janet Nugraha Jusak 2020 TLR10 and Its Unique Anti Inflammatory Properties and Potential Use as a Target in Therapeutics Immune Network 20 3 e21 doi 10 4110 in 2020 20 e21 ISSN 1598 2629 PMC 7327153 PMID 32655969 Su Si Biao Tao Lin Deng Ze Ping Chen Wen Qin Shan Yu Jiang Hai Xing April 2021 TLR10 Insights controversies and potential utility as a therapeutic target Scandinavian Journal of Immunology 93 4 e12988 doi 10 1111 sji 12988 ISSN 0300 9475 PMID 33047375 Hess NJ Jiang S Li X Guan Y Tapping RI Jan 2017 TLR10 Is a B Cell Intrinsic Suppressor of Adaptive Immune Responses Journal of Immunology 198 2 699 707 doi 10 4049 jimmunol 1601335 PMC 5225023 PMID 27956526 Govindaraj RG Manavalan B Lee G Choi S September 2010 Molecular Modeling Based Evaluation of hTLR10 and Identification of Potential Ligands in Toll Like Receptor Signaling PLOS ONE 5 9 e12713 Bibcode 2010PLoSO 512713G doi 10 1371 journal pone 0012713 PMC 2943521 PMID 20877634 Sartorius R Trovato M Manco R D Apice L De Berardinis P October 2021 Exploiting viral sensing mediated by Toll like receptors to design innovative vaccines npj Vaccines 6 1 127 doi 10 1038 s41541 021 00391 8 PMC 8553822 PMID 34711839 Entrez Gene TLR10 toll like receptor 10 Further reading EditLien E Ingalls RR 2002 Toll like receptors Crit Care Med 30 1 Suppl S1 11 doi 10 1097 00003246 200201001 00001 PMID 11782555 External links EditToll Like Receptor 10 at the U S National Library of Medicine Medical Subject Headings MeSH Overview of all the structural information available in the PDB for UniProt Q9BXR5 Toll like receptor 10 at the PDBe KB nbsp This article on a gene on human chromosome 4 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Toll like receptor 10 amp oldid 1174328374, wikipedia, wiki, book, books, library,
