Toll-like receptor 8 (TLR8) is a key component of innate and adaptive immunity [, , ]. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. It acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response []. TLR8 has been shown to recognise different types of ligands such as viral or bacterial ssRNA, as well as small synthetic molecules. Activation by ligands is species-specific, varying among non-rodents and rodents [, ].
Interferon regulatory factor 5 (IRF5) is a transcription factor involved in the induction of interferons IFNA and INFB and inflammatory cytokines upon virus infection []. It is activated by TLR7 or TLR8 signalling []. Its structure has been revealed []. Variations of the IRF5 gene affects the susceptibility of a few diseases, such as inflammatory bowel disease 14 (IBD14) [], systemic lupus erythematosus 10 (SLEB10) []and Rheumatoid arthritis (RA).
In humans, TASL (TLR adaptor interacting with SLC15A4 on the lysosome) is encoded by CXorf21 that is associated with systemic lupus erythematosus []. It is an immune adaptor that is required for recruitment and activation of IRF5 by TLR7, TLR8 and TLR9, in mechanistic analogy to IRF3 and its three adaptors STING, MAVS and TRIF. TASL interacts with the endolysosomal transporter SLC15A4; the SLC15A4-TASL complex is required for endolysosomal TLR signalling. TASL contains a pLxIS motif that is important for its function [].
