The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TLR8  -  toll-like receptor 8

Homo sapiens

Synonyms: CD288, Toll-like receptor 8, UNQ249/PRO286
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TLR8


High impact information on TLR8

  • We show that RNA signals through human TLR3, TLR7, and TLR8, but incorporation of modified nucleosides m5C, m6A, m5U, s2U, or pseudouridine ablates activity [3].
  • Similar observation were obtained in human TLR8-expressing monocyte-derived DC (moDC) using neutralizing anti-IFNAR2 antibodies, although results also pointed to a possible involvement of IFN-lambda1 (also known as IL-29) [4].
  • In addition, TLR2, TLR5 and TLR8 modulate the suppressive activity of naturally occurring CD25(+)CD4(+) regulatory T cells [5].
  • Our evidence indicates that such TLR8-mediated neuronal responses do not involve the canonical TLR-NF-kappaB signaling pathway [6].
  • Agonist stimulation of TLR8 in cultured cortical neurons causes inhibition of neurite outgrowth and induces apoptosis in a dissociable manner [6].

Biological context of TLR8


Anatomical context of TLR8

  • We have also shown that TLR8 is localized predominantly in the endoplasmic reticulum but that signaling is completely abolished by an inhibitor of vesicle-type H(+) ATPases [8].
  • Although the natural ligands for TLR7 and TLR8 have not yet been identified, our results suggest that eosinophil TLR7/8 systems represent a potentially important mechanism of a host-defensive role against viral infection and mechanism linking exacerbation of allergic inflammation and viral infection [11].
  • Subsequently we show that cellular activation by loxoribine and resiquimod (R-848), a stimulus for TLR7 and TLR8, depends on acidification and maturation of endosomes and targets MyD88 to vesicular structures with lysosomal characteristics [12].
  • Adoptive transfer of TLR8 ligand-stimulated Treg cells into tumor-bearing mice enhanced anti-tumor immunity [13].
  • Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells [7].

Associations of TLR8 with chemical compounds

  • A second region, centered on an aspartic acid residue in leucine-rich repeat 17, is also required for TLR8 function [8].
  • However, TLR8 activation by R-848 and TLR2 activation by [S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-R-Cys-S-Ser-Lys4-OH, trihydrochloride)] were not inhibited by chloroquine, whereas TLR9 activation by CpG oligodeoxynucleotides was abolished [14].
  • The small antitumoral immune response modifier imiquimod interacts with adenosine receptor signaling in a TLR7- and TLR8-independent fashion [15].
  • We demonstrate that co-incubation of R-848 with thymidine homopolymer oligodeoxynucleotides (ODN) significantly increased activity of R-848 on TLR8-expressing HEK 293 cells, but abolished TLR7-mediated signaling [16].
  • These results demonstrate an unexpected plasticity in the ligand specificities of TLR7 and TLR8, and suggest a novel sequence-selective interaction between these receptors and synthetic phosphorothioate ODN [16].

Other interactions of TLR8

  • The other TLRs that are evolutionarily closely related and highly homologous are TLR7, TLR8, and TLR9 [17].
  • Here we found that TLRs (e.g. TLR4, TLR7 and TLR8) were expressed by freshly isolated human bone marrow (BM) hematopoietic CD34+ progenitor cells [9].
  • We describe a mechanism linking Toll-like receptor (TLR) 8 signaling to the control of Treg cell function, in which synthetic and natural ligands for human TLR8 can reverse Treg cell function [13].
  • After 3 days of illness onset, only TLR3 and TLR8 mRNA expressions were still significantly (P<0.05) increased in 59% (44/75) children with diarrhoea [18].
  • Detailed analysis of the interaction between Btk and TLR8 demonstrates that the presence of both Box 2 and 3 motifs in the Toll/interleukin-1 receptor domain was required for the interaction [19].

Analytical, diagnostic and therapeutic context of TLR8

  • The cross-talk between ODNs, IRMs, and TLR7 and TLR8 uncovered by this study may have practical implications in the field of microbial infections, vaccination, and tumor therapy [20].
  • Herein we report the molecular cloning and characterization of three novel human Toll-like receptors (hTLRs) designated hTLR7, hTLR8, and hTLR9 [21].


  1. Administration of a dual toll-like receptor 7 and toll-like receptor 8 agonist protects against influenza in rats. Hammerbeck, D.M., Burleson, G.R., Schuller, C.J., Vasilakos, J.P., Tomai, M., Egging, E., Cochran, F.R., Woulfe, S., Miller, R.L. Antiviral Res. (2007) [Pubmed]
  2. TLR8 and TLR7 are involved in the host's immune response to human parechovirus 1. Triantafilou, K., Vakakis, E., Orthopoulos, G., Ahmed, M.A., Schumann, C., Lepper, P.M., Triantafilou, M. Eur. J. Immunol. (2005) [Pubmed]
  3. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Karikó, K., Buckstein, M., Ni, H., Weissman, D. Immunity (2005) [Pubmed]
  4. A type I interferon autocrine-paracrine loop is involved in Toll-like receptor-induced interleukin-12p70 secretion by dendritic cells. Gautier, G., Humbert, M., Deauvieau, F., Scuiller, M., Hiscott, J., Bates, E.E., Trinchieri, G., Caux, C., Garrone, P. J. Exp. Med. (2005) [Pubmed]
  5. Expression and function of Toll-like receptors in T lymphocytes. Kabelitz, D. Curr. Opin. Immunol. (2007) [Pubmed]
  6. Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. Ma, Y., Li, J., Chiu, I., Wang, Y., Sloane, J.A., L??, J., Kosaras, B., Sidman, R.L., Volpe, J.J., Vartanian, T. J. Cell Biol. (2006) [Pubmed]
  7. Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells. Levy, O., Suter, E.E., Miller, R.L., Wessels, M.R. Blood (2006) [Pubmed]
  8. Conserved Features in the Extracellular Domain of Human Toll-like Receptor 8 Are Essential for pH-dependent Signaling. Gibbard, R.J., Morley, P.J., Gay, N.J. J. Biol. Chem. (2006) [Pubmed]
  9. Signaling through Toll-like Receptor 7/8 Induces the Differentiation of Human Bone Marrow CD34+ Progenitor Cells along the Myeloid Lineage. Sioud, M., Fl??isand, Y., Forfang, L., Lund-Johansen, F. J. Mol. Biol. (2006) [Pubmed]
  10. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Du, X., Poltorak, A., Wei, Y., Beutler, B. Eur. Cytokine Netw. (2000) [Pubmed]
  11. Expression and function of Toll-like receptors in eosinophils: activation by Toll-like receptor 7 ligand. Nagase, H., Okugawa, S., Ota, Y., Yamaguchi, M., Tomizawa, H., Matsushima, K., Ohta, K., Yamamoto, K., Hirai, K. J. Immunol. (2003) [Pubmed]
  12. The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily. Heil, F., Ahmad-Nejad, P., Hemmi, H., Hochrein, H., Ampenberger, F., Gellert, T., Dietrich, H., Lipford, G., Takeda, K., Akira, S., Wagner, H., Bauer, S. Eur. J. Immunol. (2003) [Pubmed]
  13. Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Peng, G., Guo, Z., Kiniwa, Y., Voo, K.S., Peng, W., Fu, T., Wang, D.Y., Li, Y., Wang, H.Y., Wang, R.F. Science (2005) [Pubmed]
  14. Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Lee, J., Chuang, T.H., Redecke, V., She, L., Pitha, P.M., Carson, D.A., Raz, E., Cottam, H.B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  15. The small antitumoral immune response modifier imiquimod interacts with adenosine receptor signaling in a TLR7- and TLR8-independent fashion. Schön, M.P., Schön, M., Klotz, K.N. J. Invest. Dermatol. (2006) [Pubmed]
  16. Modulating responsiveness of human TLR7 and 8 to small molecule ligands with T-rich phosphorothiate oligodeoxynucleotides. Jurk, M., Kritzler, A., Schulte, B., Tluk, S., Schetter, C., Krieg, A.M., Vollmer, J. Eur. J. Immunol. (2006) [Pubmed]
  17. The Functional Effects of Physical Interactions among Toll-like Receptors 7, 8, and 9. Wang, J., Shao, Y., Bennett, T.A., Shankar, R.A., Wightman, P.D., Reddy, L.G. J. Biol. Chem. (2006) [Pubmed]
  18. Expression of Toll-like receptors and their association with cytokine responses in peripheral blood mononuclear cells of children with acute rotavirus diarrhoea. Xu, J., Yang, Y., Sun, J., Ding, Y., Su, L., Shao, C., Jiang, B. Clin. Exp. Immunol. (2006) [Pubmed]
  19. Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4. Jefferies, C.A., Doyle, S., Brunner, C., Dunne, A., Brint, E., Wietek, C., Walch, E., Wirth, T., O'Neill, L.A. J. Biol. Chem. (2003) [Pubmed]
  20. Oligodeoxynucleotides Differentially Modulate Activation of TLR7 and TLR8 by Imidazoquinolines. Gorden, K.K., Qiu, X., Battiste, J.J., Wightman, P.P., Vasilakos, J.P., Alkan, S.S. J. Immunol. (2006) [Pubmed]
  21. Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9. Chuang, T.H., Ulevitch, R.J. Eur. Cytokine Netw. (2000) [Pubmed]
WikiGenes - Universities