Department of Basic Sciences, Division of Histology and Immunology, Faculty of Medicine Tunis, Tunis El Manar University, Tunis 1068, Tunisia.
Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Novara, Italy.
Semin Arthritis Rheum. 2021 Jun;51(3):513-522. doi: 10.1016/j.semarthrit.2021.03.004. Epub 2021 Mar 4.
The incidence of autoimmune diseases is increasing worldwide, thus stimulating studies on their etiopathogenesis, derived from a complex interaction between genetic and environmental factors. Genetic association studies have shown the PTPN22 gene as a shared genetic risk factor with implications in multiple autoimmune disorders. By encoding a protein tyrosine phosphatase expressed by the majority of cells belonging to the innate and adaptive immune systems, the PTPN22 gene may have a fundamental role in the development of immune dysfunction. PTPN22 polymorphisms are associated with rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, and many other autoimmune conditions. In this review, we discuss the progress in our understanding of how PTPN22 impacts autoimmunity in both humans and animal models. In addition, we highlight the pathogenic significance of the PTPN22 gene, with particular emphasis on its role in T and B cells, and its function in innate immune cells, such as monocytes, dendritic and natural killer cells. We focus particularly on the complexity of PTPN22 interplay with biological processes of the immune system. Findings highlight the importance of studying the function of disease-associated PTPN22 variants in different cell types and open new avenues of investigation with the potential to drive further insights into mechanisms of PTPN22. These new insights will reveal important clues to the molecular mechanisms of prevalent autoimmune diseases and propose new potential therapeutic targets.
自身免疫性疾病的发病率在全球范围内呈上升趋势，因此激发了对其病因发病机制的研究，这些研究源自遗传和环境因素之间的复杂相互作用。遗传关联研究表明，PTPN22 基因是与多种自身免疫性疾病相关的共同遗传风险因素。该基因编码一种由先天和适应性免疫系统的大多数细胞表达的蛋白酪氨酸磷酸酶，在免疫功能障碍的发展中可能具有重要作用。PTPN22 多态性与类风湿关节炎、1 型糖尿病、系统性红斑狼疮和许多其他自身免疫性疾病有关。在这篇综述中，我们讨论了我们对 PTPN22 如何影响人类和动物模型中自身免疫的理解进展。此外，我们强调了 PTPN22 基因的致病意义，特别强调了其在 T 和 B 细胞中的作用及其在先天免疫细胞（如单核细胞、树突状细胞和自然杀伤细胞）中的功能。我们特别关注 PTPN22 与免疫系统生物过程相互作用的复杂性。研究结果强调了研究不同细胞类型中与疾病相关的 PTPN22 变体功能的重要性，并为进一步深入研究 PTPN22 机制开辟了新的研究途径，具有潜在的推动作用。这些新的见解将为常见自身免疫性疾病的分子机制提供重要线索，并提出新的潜在治疗靶点。
