TLR9
Toll-like receptor 9 is a protein that in humans is encoded by the TLR9 gene.[1] TLR9 has also been designated as CD289 (cluster of differentiation 289). It is a member of the toll-like receptor (TLR) family.
Function
The TLR family plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are named for the high degree of conservation in structure and function seen between mammalian TLRs and the Drosophila transmembrane protein Toll. TLRs are transmembrane proteins, expressed on the cell surface and the endocytic compartment and recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents and initiate signalling to induce production of cytokines necessary for the innate immunity and subsequent adaptive immunity. The various TLRs exhibit different patterns of expression. This gene is preferentially expressed in immune cell rich tissues, such as spleen, lymph node, bone marrow and peripheral blood leukocytes. Studies in mice and humans indicate that this receptor mediates cellular response to unmethylated CpG dinucleotides in bacterial DNA to mount an innate immune response.[2]
TLR9 recognizes unmethylated CpG sequences in DNA molecules. CpG sites are relatively rare (~1%) on vertebrate genomes in comparison to bacterial genomes or viral DNA. TLR9 is expressed by numerous cells of the immune system such as B lymphocytes, monocytes, natural killer (NK) cells, and plasmacytoid dendritic cells. TLR9 is expressed intracellularly, within the endosomal compartments and functions to alert the immune system of viral and bacterial infections by binding to DNA rich in CpG motifs. TLR9 signals leads to activation of the cells initiating pro-inflammatory reactions that result in the production of cytokines such as type-I interferon and IL-12.
Clinical significance
There are new immunomodulatory treatments undergoing testing which involve the administration of artificial DNA oligonucleotides containing the CpG motif. CpG DNA has applications in treating allergies such as asthma,[3] immunostimulation against cancer,[4] immunostimulation against pathogens, and as adjuvants in vaccines.[5]
Protein interactions
- TLR9 has been shown to interact with RNF216.[6]
- It can be activated by CpG Oligodeoxynucleotides such as Agatolimod.
References
- ↑ Du X, Poltorak A, Wei Y, Beutler B (Dec 2000). "Three novel mammalian toll-like receptors: gene structure, expression, and evolution". Eur Cytokine Netw 11 (3): 362–71. PMID 11022119.
- ↑ "Entrez Gene: TLR9 toll-like receptor 9".
- ↑ Kline JN (July 2007). "Eat dirt: CpG DNA and immunomodulation of asthma". Proc Am Thorac Soc 4 (3): 283–8. doi:10.1513/pats.200701-019AW. PMC 2647631. PMID 17607014.
- ↑ Thompson JA, Kuzel T, Bukowski R, Masciari F, Schmalbach T (July 2004). "Phase Ib trial of a targeted TLR9 CpG immunomodulator (CPG 7909) in advanced renal cell carcinoma (RCC)". Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition) 22 (14S).
- ↑ Klinman DM (2006). "Adjuvant activity of CpG oligodeoxynucleotides". Int. Rev. Immunol. 25 (3-4): 135–54. doi:10.1080/08830180600743057. PMID 16818369.
- ↑ Chuang TH, Ulevitch RJ (May 2004). "Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors". Nat. Immunol. 5 (5): 495–502. doi:10.1038/ni1066. PMID 15107846.
Further reading
- Lien E, Ingalls RR (2002). "Toll-like receptors.". Crit. Care Med. 30 (1 Suppl): S1–11. doi:10.1097/00003246-200201001-00001. PMID 11782555.
- Kaisho T, Akira S (2002). "Toll-like receptors as adjuvant receptors.". Biochim. Biophys. Acta 1589 (1): 1–13. doi:10.1016/S0167-4889(01)00182-3. PMID 11909637.
External links
- TLR9 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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