Division of Cellular Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
Nat Rev Rheumatol. 2014 Oct;10(10):602-11. doi: 10.1038/nrrheum.2014.109. Epub 2014 Jul 8.
PTPN22 encodes a tyrosine phosphatase that is expressed by haematopoietic cells and functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signalling and by selectively promoting type I interferon responses after activation of myeloid-cell pattern-recognition receptors. A single nucleotide polymorphism of PTPN22, 1858C>T (rs2476601), disrupts an interaction motif in the protein, and is the most important non-HLA genetic risk factor for rheumatoid arthritis and the second most important for juvenile idiopathic arthritis. PTPN22 exemplifies a shared autoimmunity gene, affecting the pathogenesis of systemic lupus erythematosus, vasculitis and other autoimmune diseases. In this Review, we explore the role of PTPN22 in autoimmune connective tissue disease, with particular emphasis on candidate-gene and genome-wide association studies and clinical variability of disease. We also propose a number of PTPN22-dependent functional models of the pathogenesis of autoimmune diseases.
PTPN22 编码一种酪氨酸磷酸酶，在造血细胞中表达，通过抑制 T 细胞受体信号和在髓样细胞模式识别受体激活后选择性促进 I 型干扰素反应，作为免疫稳态的关键调节剂发挥作用。PTPN22 的单核苷酸多态性 1858C>T（rs2476601）破坏了蛋白质中的一个相互作用基序，是类风湿关节炎最重要的非 HLA 遗传风险因素，也是青少年特发性关节炎的第二大遗传风险因素。PTPN22 是自身免疫性疾病的一个共同的易感基因，影响系统性红斑狼疮、血管炎和其他自身免疫性疾病的发病机制。在这篇综述中，我们探讨了 PTPN22 在自身免疫性结缔组织疾病中的作用，特别强调了候选基因和全基因组关联研究以及疾病的临床变异性。我们还提出了一些 PTPN22 依赖性自身免疫性疾病发病机制的功能模型。
