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Gene Review

TLR7  -  toll-like receptor 7

Homo sapiens

Synonyms: Toll-like receptor 7, UNQ248/PRO285
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Disease relevance of TLR7

  • Collectively, our results show that conjugating HIV Gag protein to a TLR7/8 agonist is an effective way to elicit broad-based adaptive immunity in NHPs [1].
  • In contrast, LC do not directly sense TLR7/8 ligands and LPS from Gram-negative bacteria, which signals through TLR4 [2].
  • Notably, IFN synthesis of PDC activated by the TLR7 and TLR9 agonists resiquimod (R848) and CpG oligodeoxynucleotide 2216 is switched off by subsequent infection by RSV A2 and measles virus [3].
  • Detection of the "molecular signature" for RNA viruses including influenza has been attributed to TLR3, TLR7, and TLR8 [4].
  • In this study we show that mainly TLR8 and also TLR7 act as the host sensors for human parechovirus 1, a single-stranded RNA (ssRNA) virus [5].
  • Our data suggest that the c.1-120G TLR7 allele offers protection from the development of inflammation and fibrosis in male patients with chronic HCV-infection [6].

High impact information on TLR7

  • Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7 [7].
  • TLR9 and TLR7 also had dramatic effects on clinical disease in lupus-prone mice [8].
  • In contrast, TLR7-deficient mice had ameliorated disease, decreased lymphocyte activation, and decreased serum IgG [8].
  • We show that RNA signals through human TLR3, TLR7, and TLR8, but incorporation of modified nucleosides m5C, m6A, m5U, s2U, or pseudouridine ablates activity [9].
  • In this issue of Immunity, Kariko et al (2005) suggest that the innate immune recognition of RNA by TLR3, TLR7, or TLR8 is in fact controlled by modification of nucleotides, including methylation [10].

Chemical compound and disease context of TLR7


Biological context of TLR7

  • NHPs immunized with HIV Gag protein and a TLR7/8 agonist or a TLR9 ligand [CpG oligodeoxynucleotides (CpG ODN)] had significantly increased Gag-specific T helper 1 and antibody responses, compared with animals immunized with HIV Gag protein alone [1].
  • Collectively, the data indicate for the first time that human BM CD34+ progenitor cells constitutively express functional TLR7/TLR8, whose ligation can induce leukopoiesis without the addition of any exogenous cytokines [13].
  • Culture with TLR7- and TLR9-ligands saves HMCL from serum-deprivation or dexamethasone-induced apoptosis [14].
  • The results implicate involvement of TLRs, particularly TLR7, and type 1 specific interferon signaling in the pathogenesis of BA, especially in early stage, which is associated with upregulation of inflammatory cytokines IL-8.Laboratory Investigation (2007) 87, 66-74. doi:10.1038/labinvest.3700490; published online 30 October 2006 [15].
  • TLR7 and TLR8 each have three exons, two of which have coding function, and lie in close proximity to one another at Xp22, alongside a pseudogene [16].

Anatomical context of TLR7


Associations of TLR7 with chemical compounds

  • In summary, we present evidence that guanosine analogs activate immune cells via TLR7 by a pathway that requires endosomal maturation [21].
  • 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 [22].
  • Stimulation of chicken TLR7 with R848 was chloroquine sensitive, suggesting signalling within an endosomal compartment, as for mammalian TLR7 [23].
  • The chicken TLR7 gene encodes a 1047-amino-acid protein with 62% identity to human TLR7 and a conserved pattern of predicted leucine-rich repeats [23].
  • Viral inhibition correlated with the ability of the TLR7/8 agonist to stimulate type I interferon (IFN) and other cytokines such as tumor necrosis factor-alpha, interleukin-12, and IFN-gamma from rat peripheral blood mononuclear cells [4].

Physical interactions of TLR7

  • TLR3 has been shown to bind viral dsRNA whereas TLR7 and TLR8 are receptors for viral single-stranded RNA [24].

Co-localisations of TLR7

  • Despite their using distinct regulatory elements for intracellular localization, TLR3 was found to co-localize with TLR7 [25].

Regulatory relationships of TLR7

  • The murine TLR8 that does not respond to any known human TLR8 agonists also inhibits both murine and human TLR7 [26].
  • RESULTS: TLR-3 and TLR-7 were highly expressed in RA synovium [27].
  • CLL cells (especially those with high endogenous expression of CD38) responded to TLR7-activating imidazoquinolines and guanosine analogs by increasing costimulatory molecule expression, producing inflammatory cytokines, and becoming more sensitive to killing by cytotoxic effectors [28].
  • TLR7 has sense Alu elements in its 3'UTR region, making it susceptible to the regulation of other protein-coding or non-coding RNAs with antisense Alu elements [29].

Other interactions of TLR7

  • 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 [20].
  • In addition, selective regulation of TLR7 expression in PDC and B cells by CpG ODN revealed TLR7 as a candidate TLR potentially involved in modulating the recognition of CpG motifs [19].
  • In addition, keratinocytes ex vivo display TLR1-5, TLR7, and TLR10 [2].
  • IRF5 and IRF7, therefore, emerge from these studies as critical mediators of TLR7 signaling [30].
  • Plasmacytoid DC (pDC) express TLR7 and TLR9 and release proinflammatory cytokines in response to imiquimod and IFN-alpha in response to CpG oligonucleotides. mDC1 are strong inducers of T cell proliferation, while pDC hardly induce any T cell proliferation. mDC2 have an intermediate T cell-stimulatory capacity [31].

Analytical, diagnostic and therapeutic context of TLR7


  1. HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates. Wille-Reece, U., Flynn, B.J., Loré, K., Koup, R.A., Kedl, R.M., Mattapallil, J.J., Weiss, W.R., Roederer, M., Seder, R.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. Human Langerhans Cells Express a Specific TLR Profile and Differentially Respond to Viruses and Gram-Positive Bacteria. Flacher, V., Bouschbacher, M., Verron??se, E., Massacrier, C., Sisirak, V., Berthier-Vergnes, O., de Saint-Vis, B., Caux, C., Dezutter-Dambuyant, C., Lebecque, S., Valladeau, J. J. Immunol. (2006) [Pubmed]
  3. Inhibition of toll-like receptor 7- and 9-mediated alpha/beta interferon production in human plasmacytoid dendritic cells by respiratory syncytial virus and measles virus. Schlender, J., Hornung, V., Finke, S., Günthner-Biller, M., Marozin, S., Brzózka, K., Moghim, S., Endres, S., Hartmann, G., Conzelmann, K.K. J. Virol. (2005) [Pubmed]
  4. 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]
  5. 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]
  6. A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection. Schott, E., Witt, H., Neumann, K., Taube, S., Oh, D.Y., Schreier, E., Vierich, S., Puhl, G., Bergk, A., Halangk, J., Weich, V., Wiedenmann, B., Berg, T. J. Hepatol. (2007) [Pubmed]
  7. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Hornung, V., Guenthner-Biller, M., Bourquin, C., Ablasser, A., Schlee, M., Uematsu, S., Noronha, A., Manoharan, M., Akira, S., de Fougerolles, A., Endres, S., Hartmann, G. Nat. Med. (2005) [Pubmed]
  8. Toll-like Receptor 7 and TLR9 Dictate Autoantibody Specificity and Have Opposing Inflammatory and Regulatory Roles in a Murine Model of Lupus. Christensen, S.R., Shupe, J., Nickerson, K., Kashgarian, M., Flavell, R.A., Shlomchik, M.J. Immunity (2006) [Pubmed]
  9. 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]
  10. TLR ignores methylated RNA? Ishii, K.J., Akira, S. Immunity (2005) [Pubmed]
  11. Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection. Horsmans, Y., Berg, T., Desager, J.P., Mueller, T., Schott, E., Fletcher, S.P., Steffy, K.R., Bauman, L.A., Kerr, B.M., Averett, D.R. Hepatology (2005) [Pubmed]
  12. Apoptotic Responses in Squamous Carcinoma and Epithelial Cells to Small-Molecule Toll-like Receptor Agonists Evaluated with Automated Cytometry. Inglefield, J.R., Larson, C.J., Gibson, S.J., Lebrec, H., Miller, R.L. Journal of biomolecular screening : the official journal of the Society for Biomolecular Screening. (2006) [Pubmed]
  13. 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]
  14. Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors. Jego, G., Bataille, R., Geffroy-Luseau, A., Descamps, G., Pellat-Deceunynck, C. Leukemia (2006) [Pubmed]
  15. Expression of toll-like receptors and type 1 interferon specific protein MxA in biliary atresia. Huang, Y.H., Chou, M.H., Du, Y.Y., Huang, C.C., Wu, C.L., Chen, C.L., Chuang, J.H. Lab. Invest. (2007) [Pubmed]
  16. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Du, X., Poltorak, A., Wei, Y., Beutler, B. Eur. Cytokine Netw. (2000) [Pubmed]
  17. 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]
  18. Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type I IFN. Bekeredjian-Ding, I.B., Berkeredjian-Ding, I.B., Wagner, M., Hornung, V., Giese, T., Schnurr, M., Endres, S., Hartmann, G. J. Immunol. (2005) [Pubmed]
  19. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. Hornung, V., Rothenfusser, S., Britsch, S., Krug, A., Jahrsdörfer, B., Giese, T., Endres, S., Hartmann, G. J. Immunol. (2002) [Pubmed]
  20. 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]
  21. 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]
  22. 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]
  23. Identification and characterization of a functional, alternatively spliced Toll-like receptor 7 (TLR7) and genomic disruption of TLR8 in chickens. Philbin, V.J., Iqbal, M., Boyd, Y., Goodchild, M.J., Beal, R.K., Bumstead, N., Young, J., Smith, A.L. Immunology (2005) [Pubmed]
  24. IFN-alpha enhances TLR3-mediated antiviral cytokine expression in human endothelial and epithelial cells by up-regulating TLR3 expression. Tissari, J., Sirén, J., Meri, S., Julkunen, I., Matikainen, S. J. Immunol. (2005) [Pubmed]
  25. TLR3 and TLR7 are targeted to the same intracellular compartments by distinct regulatory elements. Nishiya, T., Kajita, E., Miwa, S., Defranco, A.L. J. Biol. Chem. (2005) [Pubmed]
  26. 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]
  27. The expression of toll-like receptors 3 and 7 in rheumatoid arthritis synovium is increased and costimulation of toll-like receptors 3, 4, and 7/8 results in synergistic cytokine production by dendritic cells. Roelofs, M.F., Joosten, L.A., Abdollahi-Roodsaz, S., van Lieshout, A.W., Sprong, T., van den Hoogen, F.H., van den Berg, W.B., Radstake, T.R. Arthritis Rheum. (2005) [Pubmed]
  28. Immunomodulatory effects of Toll-like receptor-7 activation on chronic lymphocytic leukemia cells. Spaner, D.E., Shi, Y., White, D., Mena, J., Hammond, C., Tomic, J., He, L., Tomai, M.A., Miller, R.L., Booth, J., Radvanyi, L. Leukemia (2006) [Pubmed]
  29. A gene expression restriction network mediated by sense and antisense Alu sequences located on protein-coding messenger RNAs. Liang, K.H., Yeh, C.T. BMC. Genomics. (2013) [Pubmed]
  30. The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling. Schoenemeyer, A., Barnes, B.J., Mancl, M.E., Latz, E., Goutagny, N., Pitha, P.M., Fitzgerald, K.A., Golenbock, D.T. J. Biol. Chem. (2005) [Pubmed]
  31. Different roles for human lung dendritic cell subsets in pulmonary immune defense mechanisms. Demedts, I.K., Bracke, K.R., Maes, T., Joos, G.F., Brusselle, G.G. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  32. 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]
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