Laboratory of Translational Immunology, Department of Immunology, University Medical Centre Utrecht, The Netherlands.
Section Complex Genetics, Department of Medical Genetics, University Medical Centre Utrecht, The Netherlands.
Clin Immunol. 2014 Jan;150(1):31-42. doi: 10.1016/j.clim.2013.11.007. Epub 2013 Nov 19.
Inhibitory receptors are thought to be important in balancing immune responses. The general assumption is that lack of inhibition predisposes for autoimmune diseases. As reviewed here, various experimental and clinical data support this assumption. However, in humans genetic evidence implicates only a limited number of inhibitory receptors. GWAS have established common variation in a few inhibitory receptor genes, such as FCγRIIB, PD-1 and CTLA-4 as risk factors. The question arises whether inhibitory receptor function is a major determinant of autoimmune disease. In this respect, the finding that genetic variation in CSK and PTPN22 is strongly associated with multiple autoimmune diseases is of interest. We propose a model in which the molecules encoded by these genes are downstream of inhibitory receptors. We conclude that common genetic variation of inhibitory receptors, with few exceptions, is not a determining factor for autoimmunity in humans. However, common downstream signaling pathways are.
抑制性受体被认为在平衡免疫反应中起着重要作用。一般假设是缺乏抑制作用会导致自身免疫性疾病。正如这里所综述的，各种实验和临床数据支持这一假设。然而，在人类中，遗传证据仅暗示了少数抑制性受体。全基因组关联研究已经确定了几个抑制性受体基因（如 FCγRIIB、PD-1 和 CTLA-4）中的常见变异是风险因素。问题是抑制性受体功能是否是自身免疫性疾病的主要决定因素。在这方面，有趣的是，CSK 和 PTPN22 基因中的遗传变异与多种自身免疫性疾病强烈相关。我们提出了一个模型，其中这些基因编码的分子是抑制性受体的下游产物。我们得出结论，除了少数例外，抑制性受体的常见遗传变异不是人类自身免疫的决定因素。然而，常见的下游信号通路是。
