TLR10- cluster of differentiation 290
ByStephen Jones
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Toll-like receptor 10 (TLR10) often known as CD290 (cluster of differentiation 290), is the most recently identified human homolog of the Drosophila TOLL protein. Human TLR10 is an orphan member of the Toll-like receptor family that recognizes pathogen-associated molecular pattern. Like other members of the TLR family, TLR10 contains a signal peptide, multiple leucine-rich repeats, a cysteine-rich domain, a transmembrane domain, and a cytoplasmic TOLL interleukin-1 receptor domain. The human TLR10 gene occupies 3,269 bases arranged in three exons on the short arm of chromosome 4 (4p14) and encodes an 811-amino acid protein, approximately 50% identical to TLR1 and to TLR6. TLR10 is most closely related to TLR1 and TLR6 with 48% and 46% overall amino acid identity, respectively. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene (1).
In vivo, TLR10 mRNA expression is highest in immune system-related tissues including spleen, lymph node, thymus, tonsil. TLR10 mRNA is most highly expressed on B cells. In vitro, TLR10 is moderately upregulated by autocrine IFN-γ, IL-1β, IL-6, IL-10, and TNF-α in PMA-differentiated THP-1 cells. TLR10 mRNA expression in THP-1 cells is elevated after exposure to both Gram-positive and Gram-negative bacteria. Ex vivo, monocyte TLR10 expression increases while granulocyte expression decreases on exposure to Gram-negative bacteria. (2, 3)
Due to absent of its rat homologue, the natural ligand for TLR10 has not been identified yet. Genomic studies indicate that TLR10 is in the same locus that contains TLR1 and TLR6 and are also structurally similar to each other. It has been speculated that, like TLR1 and TLR6, TLR10 may form a heterodimer with TLR2 and thereby be sensitive to similar pathogen-associated molecular patterns (PAMPs). Recent studies have shown that TLR10 was not only able to homodimerize but also heterodimerize with TLRs 1 and 2. (1)
TLR10 has been identified as a potential asthma candidate gene because early life innate immune responses to ubiquitous inhaled allergens and PAMPs may influence asthma susceptibility and thus TLR10 genetic variation may often contributes to asthma risk. (4)
References:
1. The Journal of Immunology, 2005, 174: 2942-2950.
2. Chuang, T. & R.J. Ulevitch (2001) Biochim. Biophys. Acta 1518:157.
3. Zarember, K.A. & P.J. Godowski (2002) J. Immunol. 168:554.
4. Hornung, V. et al. (2002) J. Immunol. 168:4531.
IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about Toll-like receptors .
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