TLR7 gene

The TLR7 gene (TLR7Toll Like Receptor 7) is a protein-coding gene located on chromosome Xp22.2. Related signaling pathways include the MyD88-dependent endosome-initiated cascade and SARS-CoV-2 infection. The TLR7 gene is predominantly expressed in the lung, placenta and spleen and is phylogenetically related and located in close proximity to another family member, the TLR8 gene, on chromosome X.

The protein encoded by the TLR7 gene belongs to the Toll-like receptor (TLR7) family, which plays a fundamental role in the recognition of pathogens and the activation of innate immunity. TLRs are highly conserved from Drosophila to humans and show structural and functional similarities. The human TLR family comprises 11 members (TLT1-TLR11). Toll-like receptors (TLRs) are single transmembrane cell surface receptors that play a key role in the innate immune system. TLRs usually exist as homodimers and are found on immune cells, macrophages, B lymphocytes and mast cells. TLRs recognize pathogen-associated molecular patterns (PAMPs) expressed on infectious agents and mediate the production of cytokines necessary for the development of effective immunity. The different TLRs also have different expression patterns for the recognition of structural components in foreign microorganisms; for example, TLR3, -7 and -8 are essential for the recognition of single-stranded RNA viruses. TLR7 recognizes single-stranded RNA oligonucleotides containing guanosine- and uridine-rich sequences of RNA viruses, whereby this recognition takes place in the endosomes of plasmacytoid dendritic cells and B cells.

TLR7 is an endosomal receptor that plays a key role in innate and adaptive immunity (Diebold SS et al. 2004). The receptor regulates the host immune response against pathogens by recognizing uridine-containing single-stranded RNAs (ssRNAs) of viral origin or guanosine analogues (Davenne T et al. 2020; Brown GJ et al. 2022). Upon binding to agonistic ligands, dimerization occurs, bringing the TIR domains of the two molecules into direct contact, leading to recruitment of the TIR-containing downstream adaptor MYD88 through homotypic interaction. In turn, the myddosome signaling complex is formed, involving IRAK4, IRAK1, TRAF6 and TRAF3, leading to activation of the downstream transcription factors NF-kappa-B and IRF7 to induce proinflammatory cytokines and interferons, respectively (van der Made CI et al. 2020).

Diseases associated with TLR7 include Systemic Lupus Erythematosus 17 and Immunodeficiency 74, Covid19-related, X-linked.

1. Brown GJ et al. (2022) TLR7 gain-of-function genetic variation causes human lupus. Nature 605:349-356.
2. Davenne T et al. (2020) Deoxyguanosine is a TLR7 agonist. Eur J Immunol 50:56-62.
3. Diebold SS et al. (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529-1531.
4. van der Made CI et al. (2020) Presence of Genetic Variants Among Young Men With Severe COVID-19. JAMA 324:663-673.