TLR9
Toll样受体9（英语：Toll-like receptor 9）是由人类基因 TLR9 编码的蛋白质[1]，也被称为CD289（分化簇289，cluster of differentiation 289），是Toll样受体（TLR）家族的成员。
功能 编辑
TLR家族的受体在病原识别与先天免疫的激活中起着基础作用。TLRs are named for the high degree of conservation in structure and function seen between mammalian TLRs and the Drosophila transmembrane protein Toll. TLRs是呈现在细胞表面和胞内间室的跨膜蛋白，用以识别病原体呈现的病原相关分子模式（Pathogen-associated molecular patterns，PAMPs），然后启动制造先天和获得性免疫所需的细胞因子的信号。 The various TLRs exhibit different patterns of expression. 这一基因通常表达于富含免疫细胞的组织，比如脾、淋巴结、骨髓等。研究指出，在小鼠和人中的TLR9受体可响应细菌DNA中的未甲基化的CpG寡脱氧核苷酸序列来激活先天免疫应答[2]。
TLR9可以识别DNA分子中的未甲基化的CpG序列，CpG位点在脊椎动物非常稀少（~1%），但在细菌或病毒基因组中很丰富。TLR9在免疫系统的多种细胞中有表达，如B淋巴细胞、单核细胞、自然杀伤细胞（NK）和浆细胞样树突状细胞。TLR9表达于细胞内，是核内体的组分之一，其功能为当细菌或病毒感染时结合其DNA上的富CpG基序来改变免疫系统的状态。TLR9的信号会导致细胞启动炎症反应，并分泌相关细胞因子，如I型干扰素和IL-12等。
临床意义 编辑
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]
蛋白质相互作用 编辑
参考文献 编辑
- ^ Du X, Poltorak A, Wei Y, Beutler B. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw. Dec 2000, 11 (3): 362–71. PMID 11022119.
- ^ Entrez Gene: TLR9 toll-like receptor 9.
- ^ Kline JN. Eat dirt: CpG DNA and immunomodulation of asthma. Proc Am Thorac Soc. July 2007, 4 (3): 283–8. PMC 2647631
. PMID 17607014. doi:10.1513/pats.200701-019AW.
- ^ Thompson JA, Kuzel T, Bukowski R, Masciari F, Schmalbach T. 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). July 2004, 22 (14S) [2016-01-14]. （原始内容存档于2012-03-08）.
- ^ Klinman DM. Adjuvant activity of CpG oligodeoxynucleotides. Int. Rev. Immunol. 2006, 25 (3-4): 135–54. PMID 16818369. doi:10.1080/08830180600743057.
- ^ Chuang TH, Ulevitch RJ. Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat. Immunol. May 2004, 5 (5): 495–502. PMID 15107846. doi:10.1038/ni1066.
延伸阅读 编辑
- Lien E, Ingalls RR. Toll-like receptors.. Crit. Care Med. 2002, 30 (1 Suppl): S1–11. PMID 11782555. doi:10.1097/00003246-200201001-00001.
- Kaisho T, Akira S. Toll-like receptors as adjuvant receptors.. Biochim. Biophys. Acta. 2002, 1589 (1): 1–13. PMID 11909637. doi:10.1016/S0167-4889(01)00182-3.
外部链接 编辑