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J Immunol ; 174(5): 2942-50, 2005 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-15728506

RESUMO

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.


Assuntos
Antígenos de Diferenciação/fisiologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Regulação da Expressão Gênica/imunologia , Receptores de Superfície Celular/fisiologia , Receptores Imunológicos/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Animais , Antígenos CD4/genética , Antígenos CD4/metabolismo , Linhagem Celular , Glicosilação , Humanos , Glicoproteínas de Membrana/genética , Camundongos , Dados de Sequência Molecular , Fator 88 de Diferenciação Mieloide , Regiões Promotoras Genéticas , Estrutura Terciária de Proteína/genética , Ratos , Receptores de Superfície Celular/biossíntese , Receptores de Interleucina-1/genética , Homologia de Sequência de Aminoácidos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Receptor 10 Toll-Like
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