Kochi Yuta
Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 113-8655, Japan
Int Immunol. 2016 Apr;28(4):155-61. doi: 10.1093/intimm/dxw002. Epub 2016 Feb 8.
Genome-wide association studies (GWASs) for autoimmune diseases (ADs) have identified many risk loci and have provided insights into the etiology of each disease. Some of these loci, such asPTPN22,IL23RandSTAT4, are shared among different ADs, and the combination of risk loci may determine an individual's susceptibility for a disease. The majority of GWAS loci are expression quantitative trait loci (eQTLs), where disease-causing variants regulate expression of neighboring (or sometimes distant) genes. Because the eQTL effects are often cell type-specific, the incorporation of epigenetic data from disease-related cell types and tissues is expected to refine the identification of causal variants. The cumulative eQTL effects in multiple genes may influence the activity or fate of immune cells, which in turn may affect the function of the immune system in individuals. In this paper, I review the etiology of ADs by focusing on important immune cells (Th1 cells, Th17 cells and regulatory T cells), important pathways (antigen-receptor signaling and type I interferon signaling) and relevant genes identified in GWASs.
针对自身免疫性疾病（ADs）的全基因组关联研究（GWASs）已经确定了许多风险位点，并为每种疾病的病因提供了见解。其中一些位点，如蛋白酪氨酸磷酸酶非受体型22（PTPN22）、白细胞介素23受体（IL23R）和信号转导与转录激活因子4（STAT4），在不同的自身免疫性疾病中是共享的，风险位点的组合可能决定个体对某种疾病的易感性。大多数GWAS位点是表达数量性状位点（eQTLs），致病变异在这些位点调控邻近（有时是远距离）基因的表达。由于eQTL效应通常具有细胞类型特异性，因此纳入来自疾病相关细胞类型和组织的表观遗传数据有望优化因果变异的识别。多个基因中累积的eQTL效应可能影响免疫细胞的活性或命运，进而可能影响个体免疫系统的功能。在本文中，我将重点关注重要的免疫细胞（辅助性T细胞1（Th1细胞）、辅助性T细胞17（Th17细胞）和调节性T细胞）、重要的信号通路（抗原受体信号传导和I型干扰素信号传导）以及在GWASs中确定的相关基因，来综述自身免疫性疾病的病因。
