Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88.
Human TLR10 is an orphan member of the TLR family. Genomic studies indicate that TLR10 is in a locus that also contains TLR1 and TLR6, two receptors known to function as coreceptors for TLR2. We have shown that TLR10 was not only able to homodimerize but also heterodimerized with TLRs 1 and 2. In addition, unlike TLR1 and TLR6, TLR10 was expressed in a highly restricted fashion as a highly N-glycosylated protein, which we detected in B cell lines, B cells from peripheral blood, and plasmacytoid dendritic cells from tonsil. We were also able to detect TLR10 in a CD1a(+) DC subset derived from CD34(+) progenitor cells which resemble Langerhans cells in the epidermis. Although we were unable to identify a specific ligand for TLR10, by using a recombinant CD4TLR10 molecule we also demonstrated that TLR10 directly associates with MyD88, the common Toll IL-1 receptor domain adapter. Additionally, we have characterized regions in the Toll IL-1 receptor domain of TLR10 that are essential in the activation of promoters from certain inflammatory cytokines. Even though TLR10 expression has not been detected in mice, we have identified a partial genomic sequence of the TLR10 gene that was present but nonfunctional and disrupted by a retroviral insertion in all mouse strains tested. However, a complete TLR10 sequence could be detected in the rat genome, indicating that a functional copy may be preserved in this species.
Hasan
Uzma
U
Schering-Plough Research Institute, Laboratory for Immunological Research, Dardilly, France.
Chaffois
Claire
C
Gaillard
Claude
C
Saulnier
Virginie
V
Merck
Estelle
E
Tancredi
Sandra
S
Guiet
Chantal
C
Brière
Francine
F
Vlach
Jaromir
J
Lebecque
Serge
S
Trinchieri
Giorgio
G
Bates
Elizabeth E M
EE
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051201:Toll-Like Receptor 10
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D015704:CD4 Antigens; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; C499045:TIRAP protein, mouse; C475955:TLR10 protein, human; D051201:Toll-Like Receptor 10