Toll-like receptor 7

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 29.10.2020

Dieser Artikel auf Deutsch

Synonym(s)

TLR 7

Definition
This section has been translated automatically.

In evolutionary terms, TLRs are old, conserved PRRs (Pattern Recognition Receptors); Toll-like receptors are primarily used for the recognition of so-called "Pathogen Associated Molecular Patterns" (PAMPs). TLRs are transmembrane glycoproteins. Their extracellular, N-terminal domain consists of an LRR that specifically binds different ligands. A transmembrane domain follows. The signal transduction takes place through the cytoplasmic "Toll-interleukin-1 receptor homology" domain, TIR for short. This recruits molecules that also contain a TIR domain, but which may differ from TLR to TLR.

In humans, there are now 10 (TLR-1 to 10) and 12 murine (TLR-1 to 9 + 11 and 13). 6 of the human TLRs bind PAMPs extracellularly (TLR-1, 2, 4, 5, 6, 10) while 4 are only localized intracellularly (TLR-3, 7, 8 and 9).

TLRs are expressed in immune cells of the innate and also of cells of the adaptive immune system (B and T cells) as well as in various epithelial cells (e.g. intestinal epithelia). This wide distribution makes TLRs an excellent tool for both the innate and the acquired immune system. TLRs are thus responsible for the recognition of pathogens and the activation of antigen-specific acquired immunity. Through the activity of TLRs, the innate defence mechanisms (see below immunity, innate) can distinguish between "self" and "foreign". For the detection of pathogens, the TLRs need different adaptor molecules for the activation of intracellular signalling cascades such as: MyD88, TICAM-1 (TRIF), TIRAP/MAL, TRAM, and SARM.

General information
This section has been translated automatically.

The natural ligand for the dimeric receptor TLR7/TLR8 is single-stranded RNA (ssRNA), as found in viruses, but also in human cells or in the form of so-called synthetic oligoribonucleotides (ORN). Apparently, this recognition is motif dependent and less dependent on the content of guanosine (G) and uridine (U) of the ssRNA.

Extracellular ssRNA can only occur when endogenous or foreign cells have died. In any case, this condition is evaluated by the immune system as a danger signal. An inflammatory reaction is triggered via TLR7/TLR8.

Toll-like receptors play a role in the development of cancer. There is a whole range of TLR agonists. Only the topically available TLR7-agonists have proven to be useful therapeutics in tumor therapy (Wang C et al. 2015). The main target cell of TLR7 agonists are IFN-α -producing plasmacytoid dendritic cells. They are the starting point of an adaptive immune response. Besides NK cells, antigen-specific T cells are the effectors of the TLR7 agonist reaction.

Imiquimod and loxoribin are such agonists of the Toll-like receptor 7 (TLR7). Imiquimod, as a meanwhile approved preparation, has proven to be an efficient topical agent for the treatment of superficial basal cell carcinoma. A functional X-linked TLR7 rs179008/Gln11Leu polymorphism of the TLR7 receptor leads to a reduction of the clinical efficacy of Imiquimod.

Other polymorphisms of TLR7 and TLR9 are associated with the development of systemic lupus erythematosus in Asian populations.

Literature
This section has been translated automatically.

  1. Kobold S et al (2014) Modes of action of TLR7 agonists in cancer therapy. Immunotherapy 6:1085-1095
    Lee YH et al (2012) Associations between TLR polymorphisms and systemic lupus erythematosus: a systematic review and meta-analysis. Clin Exp Rheumatol 30:262-265.
  2. Piaserico S et al (2015) TLR7 Gln11Leu single nucleotide polymorphism and response to treatment with imiquimod in patients with basal cell carcinoma: a pilot study. Pharmacogenomics 16:1913-1937.
  3. Zhang L et al (2015) The TLR7 agonist Imiquimod promote the immunogenicity of mesenchymal stem cells. Biol Res 48:6.
  4. Wang C et al (2015) The TLR7 agonist induces tumor regression both by promoting CD4⁺T cells proliferation and by reversing T regulatory cell-mediated suppression via dendritic cells. Oncotarget 6:1779-1789.

Authors

Last updated on: 29.10.2020