TLR9
Toll样受体9(英語: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是呈現在細胞表面和胞內間室的跨膜蛋白,用以識別病原體呈現的病原相关分子模式(Pathogen-associated molecular patterns,PAMPs),然後啟動製造先天和获得性免疫所需的细胞因子的信號。 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
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