Toll-like receptor 10 is aprotein that in humans is encoded by theTLR10gene.[3] TLR10 has also been designated asCD290 (cluster of differentiation 290).TLR10 has not been extensively studied because it is apseudogene in mice, though all other mammalian species contain an intact copy of the TLR10 gene. Unlike other TLRs, TLR10 does not activate the immune system and has instead been shown to suppress inflammatory signaling on primary human cells.[4] This makes TLR10 unique among the TLR family. TLR10 was thought to be an "orphan" receptor, however, recent studies have identified ligands for TLR10 and these includeHIV-gp41.[5] Ligands forTLR2 are potential ligands for TLR10.[6]
The protein encoded by this gene is a member of thetoll-like receptor (TLR) family which play a fundamental role inpathogen recognition and activation ofinnate immunity. TLRs are highly conserved fromDrosophila to humans and share structural and functional similarities. They recognizepathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production ofcytokines necessary for the development of effective immunity.
TLR10 is unique among the TLR family in having an anti-inflammatory function, rather than a pro-inflammatory function. This was discovered by over-expressing TLR10 in human cell lines and using antibody-mediated engagement of the receptor on primary human cells. When TLR10 is activated in this manner, it suppresses the amount of cytokines produced, as compared to control cells. TLR10 engagement also has long-term effects onmonocyte andB cell activation/differentiation by suppressing the transcription of activation markers. TLR10's mechanism of action is not yet known but activation of the receptor has been shown to suppressNF-κB,MAP kinase andAkt signaling events stimulated by TLR andCD40 ligands.[7] The computational analysis reported that TLR10 can interact withpeptidoglycan and (triacyl) lipopeptides in concert with TLR2 (as aheterodimer).[8]
TLR10 has been transcriptionally shown to be expressed insecondary lymphoid tissues such as the spleen, lymph nodes, and tonsils. More specifically, protein level expression of TLR10 has been shown on the surface of B cells, monocytes andneutrophils; but not onT cells. B cells have the highest expression of TLR10 among these cell types but the overall expression of TLR10 is low compared to other TLRs. TLR10 has also been shown to be produced intracellularly in monocytes and neutrophils.
Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.[10]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Chuang T, Ulevitch RJ (March 2001). "Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells".Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression.1518 (1–2):157–161.doi:10.1016/s0167-4781(00)00289-x.PMID11267672.
