Toll-like receptor 10

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 adaptive immune system (B and T cells) as well as in various epithelial cells (e.g. intestinal epithelia, McDermott AJ et al. 2014; Husseinzadeh N et al. 2014). This wide distribution makes TLRs an excellent tool for the innate and 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.

Toll-like receptor (TLR)10 is the only PRR without known specific ligands and without a clear biologic function. Apparently, modulatory TLR10 signals predominantly lead to inhibitory immunological effects. If TLR10 is blocked by antagonists, increased proinflammatory cytokine production occurs, e.g. by interleukin-1β (Oosting M et al. 2014).

However, TLR10 appears to play a role in the innate immune response in viral infections, such as influenza virus infections (Lee SM et al.2014). There is evidence of an association between TLR10 and Crohn's disease.

1. Oosting M et al (2014) Human TLR10 is an anti-inflammatory pattern-recognition receptor. Proc Natl Acad Sci U S A 111:E4478-4484.
2. Lee SM et al(2014) Toll-like receptor 10 is involved in induction of innate immune responses to influenza virus infection. Proc Natl Acad Sci U S A 111:3793-3798.
3. Morgan AR et al(2012) Genetic variation withinTLR10 is associated with Crohn's disease in a New Zealand population. Hum Immunol 73:416-420.