CXCR3
趋化因子受体CXCR3是G蛋白偶连的七跨膜域受体，可选择性地与CXC趋化因子（CXCL9，CXCL10，和CXCL11）结合[1]。 CXCR3又称G蛋白偶联受体9(GPR9)和CD183。有两种变异的CXCR3受体。CXCR3－A与CXCL9， CXCL10，CXCL11结合；而CXCR3-B除了与CXCL9， CXCL10，CXCL11结合外还可以与CXCL4结合[2]。
表达
CXCR3主要表达在T细胞、自然杀伤细胞活性上[3]，有的上皮细胞和一些内皮细胞也表达CXCR3。 I型辅助T细胞（Th1）优先表达CXCR3及CCR5[3]，而II型辅助T细胞（Th2）表达CCR3和CCR4。 CXCR3与配体结合后在诱导I型辅助T细胞（Th1）迁移的同时又阻止II型辅助T细胞（Th2）的迁徙。从而增强T细胞的分化效应。
信号传递
CXCR3与其配体CXCL9， CXCL10，CXCL11的结合，能引起细胞钙离子的内流，启动肌醇磷脂3-激酶和丝裂原活化蛋白激酶（MAPK）[4]。详细的信号通路尚未确立，但与其他的趋化因子受体的信号传递有类似的激酶。
功能
CXCR3调节白细胞迁徙。CXCR3与配体相互作用引起I型辅助T细胞（Th1）的迁移，并促进I型辅助T细胞（Th1）成熟。
疾病
CXCR3可能在下列疾病中起作用，包括动脉粥样硬化[5]、多发性硬化[6]、肺纤维化[7], I型糖尿病[8]，重症肌无力、急性心脏移植排斥[9]。开发阻断CXCR3与其配体相互作用的药物可提供治疗这些疾病的新途径。
参见
参考文献
- ^ Clark-Lewis I, Mattioli I, Gong JH, Loetscher P. Structure-function relationship between the human chemokine receptor CXCR3 and its ligands. J Biol Chem. 2003 Jan 3;278(1):289-95.
- ^ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med. 2003 Jun 2;197(11):1537-49.
- ^ 3.0 3.1 Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, Koch AE, Moser B, Mackay CR. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest. 1998 Feb 15;101(4):746-54.
- ^ Smit MJ, Verdijk P, van der Raaij-Helmer EM, Navis M, Hensbergen PJ, Leurs R, Tensen CP. CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase. Blood. 2003 Sep 15;102(6):1959-65.
- ^ Mach F, Sauty A, Iarossi AS, Sukhova GK, Neote K, Libby P, Luster AD. Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells. J Clin Invest. 1999 Oct;104(8):1041-50.
- ^ Sorensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, Qin S, Rottman J, Sellebjerg F, Strieter RM, Frederiksen JL, Ransohoff RM. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest. 1999 Mar;103(6):807-15.
- ^ Jiang D, Liang J, Hodge J, Lu B, Zhu Z, Yu S, Fan J, Gao Y, Yin Z, Homer R, Gerard C, Noble PW. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J Clin Invest. 2004 Jul;114(2):291-9.
- ^ Frigerio S, Junt T, Lu B, Gerard C, Zumsteg U, Hollander GA, Piali L. Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis. Nat Med. 2002 Dec;8(12):1414-20.
- ^ Hancock WW, Lu B, Gao W, Csizmadia V, Faia K, King JA, Smiley ST, Ling M, Gerard NP, Gerard C. Requirement of the chemokine receptor CXCR3 for acute allograft rejection. J Exp Med. 2000 Nov 20;192(10):1515-20.
外部链接
- Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006 Feb 9;354(6):610-21.（页面存档备份，存于互联网档案馆）
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