Department of Oncology, University Hospital Zurich, Switzerland.
Ann N Y Acad Sci. 2012 Jun;1257:93-102. doi: 10.1111/j.1749-6632.2012.06578.x.
Genome-wide association studies have identified single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase nonreceptor type 2 (PTPN2) as a risk factor for the development of chronic inflammatory diseases, such as inflammatory bowel disease (IBD), type 1 diabetes, and rheumatoid arthritis. IBD is characterized by a breakdown of the intestinal epithelial barrier function leading to an overwhelming and uncontrolled immune response to bacterial antigens. Recent studies demonstrated that PTPN2 regulates cytokine-induced signaling pathways, epithelial barrier function, and cytokine secretion in human intestinal cells. Dysfunction of PTPN2 is also associated with impaired autophagosome formation and defective bacterial handling in intestinal cells. All of these cellular functions have been demonstrated to play a crucial role in the pathogenesis of IBD. The genetic variations within the PTPN2 gene may result in altered protein function, thereby essentially contributing to the onset and perpetuation of chronic inflammatory conditions in the intestine.
全基因组关联研究已经确定了编码蛋白酪氨酸磷酸酶非受体型 2（PTPN2）的基因座内的单核苷酸多态性是慢性炎症性疾病（如炎症性肠病（IBD）、1 型糖尿病和类风湿关节炎）发展的风险因素。IBD 的特征是肠道上皮屏障功能的破坏，导致对细菌抗原的压倒性和失控的免疫反应。最近的研究表明，PTPN2 调节细胞因子诱导的信号通路、上皮屏障功能和人肠道细胞中的细胞因子分泌。PTPN2 的功能障碍也与肠道细胞中自噬体形成受损和细菌处理缺陷有关。所有这些细胞功能都被证明在 IBD 的发病机制中起着至关重要的作用。PTPN2 基因内的遗传变异可能导致蛋白质功能改变，从而主要导致肠道慢性炎症状态的发生和持续。
