Biology:Toll-like receptor 10

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Toll-like receptor 10 is a protein that in humans is encoded by the TLR10 gene.[1] 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.[2] 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.[3] Ligands for TLR2 are potential ligands for TLR10.[4]

Function

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.[5] 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).[6]

Some ligands of TLR10 have been recently described: HIV-1 gp41, H. pylori LPS (TLR2/10), L. monocytogenes, B burgdorferi, H1N1/H5N1.[7]

Expression

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.[8]

References

  1. ↑ "Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells". Biochim Biophys Acta 1518 (1–2): 157–61. Mar 2001. doi:10.1016/s0167-4781(00)00289-x. PMID 11267672. 
  2. ↑ "TLR10 is a Negative Regulator of Both MyD88-Dependent and -Independent TLR Signaling". Journal of Immunology 196 (9): 3834–3841. May 2016. doi:10.4049/jimmunol.1502599. PMID 27022193. 
  3. ↑ 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. PMID 32655969. PMC 7327153. http://dx.doi.org/10.4110/in.2020.20.e21. 
  4. ↑ 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" (in en). Scandinavian Journal of Immunology 93 (4): e12988. doi:10.1111/sji.12988. ISSN 0300-9475. PMID 33047375. 
  5. ↑ "TLR10 Is a B Cell Intrinsic Suppressor of Adaptive Immune Responses". Journal of Immunology 198 (2): 699–707. Jan 2017. doi:10.4049/jimmunol.1601335. PMID 27956526. 
  6. ↑ "Molecular Modeling-Based Evaluation of hTLR10 and Identification of Potential Ligands in Toll-Like Receptor Signaling". PLOS ONE 5 (9): e12713. September 2010. doi:10.1371/journal.pone.0012713. PMID 20877634. Bibcode: 2010PLoSO...512713G. 
  7. ↑ "Exploiting viral sensing mediated by Toll-like receptors to design innovative vaccines". npj Vaccines 6 (1): 127. October 2021. doi:10.1038/s41541-021-00391-8. PMID 34711839. 
  8. ↑ "Entrez Gene: TLR10 toll-like receptor 10". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=81793. 

Further reading

External links




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