摘要
细胞表面糖蛋白CD6在白细胞中表达,介导T细胞穿过内皮细胞屏障。CD6参与自身免疫性疾病,包括多发性硬化症(MS)和类风湿性关节炎(RA)。CD166是CD6的生理配体,它在中枢神经系统内皮细胞、关节的胶原组织的以及滑膜成纤维细胞的细胞表面得到表达。动物模型和体外实验表明,CD166促进白细胞贩运到中枢神经系统,调节滑膜细胞与T淋巴细胞的相互作用,这可能是MS和RA的共同发病机制。近年来,全基因组关联研究(GWAS)建立了CD6和MS之间的遗传联系。单核苷酸多态性(SNP)rs17824933在CD6基因中已被识别和验证,并作为导致MS的遗传危险因素。SNP与CD4+ T细胞功能改变及CD6剪接变异体在T细胞的表达有关。其他几个独立的CD6基因多态性与疾病的易感性或临床特征如MS严重损伤恢复相关。除了发现MS的遗传相关外,CD6等位基因变异与类风湿关节炎患者的肿瘤坏死因子TNF抑制剂相关。初步数据显示,抗CD6屏蔽可能为RA的治疗银屑病的有效工具。总之,遗传相关和临床观察为CD6在自身免疫中的作用提供了新的证据。
关键词: CD6,遗传关联,多发性硬化症,T细胞、CD166、类风湿性关节炎、肿瘤坏死因子-α抑制剂,免疫
Current Drug Targets
Title:The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations
Volume: 17 Issue: 6
Author(s): David M. Kofler, Aron Farkas, Michael von Bergwelt-Baildon and David A. Hafler
Affiliation:
关键词: CD6,遗传关联,多发性硬化症,T细胞、CD166、类风湿性关节炎、肿瘤坏死因子-α抑制剂,免疫
摘要: The cell surface glycoprotein CD6 is expressed on leukocytes and mediates T cell trafficking across endothelial cell barriers. There is evidence suggesting that CD6 is implicated in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and rheumatoid arthritis (RA). CD166, the physiological ligand of CD6, is expressed on endothelial cells in the central nervous system and in the collagen tissue of joints as well as on the cell surface of synovial fibroblasts. Animal models and in vitro experiments have shown that CD166 facilitates leukocyte trafficking into the central nervous system and mediates interactions of synovial cells with T lymphocytes, thereby representing a possible common mechanism of pathogenesis in MS and RA. In recent years, genome-wide association studies (GWAS) have established a genetic link between CD6 and MS. The single nucleotide polymorphism (SNP) rs17824933 in the CD6 gene has been identified and validated as a genetic risk factor for the development of MS. The SNP is associated with altered CD4+ T cell functions and with the expression of alternative CD6 splice variants in T cells. Several other independent CD6 gene polymorphisms have been associated with disease susceptibility or with clinical features such as worse attack recovery in MS. In addition to the genetic associations found in MS, an allelic variant of the CD6 gene correlates with clinical response to tumor necrosis factor- (TNF-) inhibitors in patients with RA. Preliminary data indicate that anti-CD6 blockade may be a promising tool for the treatment of RA and psoriasis. Taken together, genetic associations and clinical observations provide new evidence for a role of CD6 in autoimmunity.
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David M. Kofler, Aron Farkas, Michael von Bergwelt-Baildon and David A. Hafler , The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations, Current Drug Targets 2016; 17 (6) . https://dx.doi.org/10.2174/1389450117666160201105934
DOI https://dx.doi.org/10.2174/1389450117666160201105934 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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