TLR8
Description
The TLR8 (toll like receptor 8) is a protein-coding gene located on chromosome X.
TLR8 is a protein encoded by the TLR8 gene in humans, also known as CD288. It belongs to the toll-like receptor (TLR) family, which plays a key role in pathogen recognition and activation of innate immunity. While TLR8 was previously thought to be nonfunctional in mice, recent research suggests it counteracts TLR7 activity. TLR8 is primarily expressed in lung and peripheral blood leukocytes, located near another TLR family member, TLR7, on chromosome X. TLR8 has been found to be expressed in hippocampal interneurons, although its function in this location remains unclear. TLR8 can recognize GU-rich single-stranded RNA, but the presence of these sequences alone is not enough to stimulate TLR8 activity.
TLR8 is an endosomal receptor that plays a crucial role in both innate and adaptive immunity. It recognizes specific RNA degradation products generated by microorganisms, which are initially processed by RNASET2. These recognized RNA products include GU-rich single-stranded RNA (GU-rich RNA) derived from viruses such as SARS-CoV-2, SARS-CoV-1, and HIV-1. Upon binding to these agonists, TLR8 undergoes dimerization, bringing the TIR domains from the two molecules into direct contact. This interaction leads to the recruitment of the TIR-containing downstream adapter MYD88 through homotypic interaction. This forms the Myddosome signaling complex involving IRAK4, IRAK1, TRAF6, and TRAF3, ultimately activating downstream transcription factors NF-kappa-B and IRF7. These activated transcription factors then induce the production of pro-inflammatory cytokines and interferons, respectively.
TLR8 is also known as CD288, IMD98, TLR-8, hTLR8.
