X chromosome reactivation perturbs intracellular self/not-self discrimination
X chromosome reactivation perturbs intracellular self/not-self discrimination
复制标题
DOI：
10.1038/icb.2009.39
复制
发表时间：
2009-10-01
影响因子：
4
通讯作者：
Forsdyke, Donald R.
中科院分区：
文献类型：
--
作者：
Forsdyke, Donald R.
新的报告表明，女性对自身免疫性疾病的易感性是基于染色体而不是激素。有人认为，如果女性重新激活失活的X染色体，将有某些X定位的基因影响免疫功能的过度表达。因此，自我/非自我辨别的正常机制可能受损，导致对自身抗原的免疫反应。然而，这些数据也与长期持有的观点一致，即细胞内自我/非自我辨别的需求推动了X染色体剂量补偿的演变。有人提出，无论细胞是在男性还是女性体内，蛋白质的浓度都被微调到它们的聚集阈值。这种平衡的破坏，由外部（例如，病毒）或内部（例如，重新激活的X染色体），产生同源聚集体，触发对各自的非自身或自身抗原的反应。因此，女性对自身免疫性疾病的易感性可能并不是因为某些免疫系统基因恰好位于X染色体上，而是因为自我/非自我的区分是X染色体剂量补偿的首要理由。Immunology and Cell Biology（2009）87，525-528; doi：10.1038/icb.2009.39; 2009年6月9日在线发表
New reports indicate a chromosomal rather than hormonal basis for the susceptibility of females to autoimmune disease. It is held that if females reactivate an inactivated X chromosome, there will be overexpression of certain X-located genes affecting immune function. Hence, normal mechanisms of self/not-self discrimination might be impaired resulting in immune reaction to self antigens. However, the data are also consistent with the long-held view that the demands of intracellular self/not-self discrimination have driven the evolution of X-chromosome dosage compensation. It was proposed that, whether cells are in male or female bodies, concentrations of proteins are fine-tuned up to their aggregation thresholds. A disruption of this equilibrium, by agents originating either externally (for example, virus) or internally (for example, reactivated X chromosome), generates homoaggregates that trigger responses against the respective not-self or self antigens. Thus, female susceptibility to autoimmune disease may not be because certain immune system genes happen to be X-located, but because self/not-self discrimination was the raison d'etre for X-chromosome dosage compensation in the first place. Immunology and Cell Biology (2009) 87, 525-528; doi: 10.1038/icb.2009.39; published online 9 June 2009