Inheritance of a coding variant of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene is associated with increased susceptibility to autoimmunity and infection. Efforts to elucidate the mechanisms by which the PTPN22-C1858T variant modulates disease risk revealed that PTPN22 performs a signaling function in multiple biochemical pathways and cell types. Capable of both enzymatic activity and adaptor functions, PTPN22 modulates signaling through antigen and innate immune receptors. PTPN22 plays roles in lymphocyte development and activation, establishment of tolerance, and innate immune cell-mediated host defense and immunoregulation. The disease-associated PTPN22-R620W variant protein is likely involved in multiple stages of the pathogenesis of autoimmunity. Establishment of a tolerant B cell repertoire is disrupted by PTPN22-R620W action during immature B cell selection, and PTPN22-R620W alters mature T cell responsiveness. However, after autoimmune attack has initiated tissue injury, PTPN22-R620W may foster inflammation through modulating the balance of myeloid cell-produced cytokines.

中文翻译：

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酪氨酸磷酸酶 PTPN22：免疫信号、发育和疾病的多功能调节剂。

蛋白酪氨酸磷酸酶非受体 22 型 (PTPN22) 基因编码变体的遗传与自身免疫和感染的易感性增加有关。阐明 PTPN22-C1858T 变体调节疾病风险的机制的努力表明 PTPN22 在多种生化途径和细胞类型中发挥信号功能。PTPN22 具有酶活性和适配器功能，可通过抗原和先天免疫受体调节信号传导。PTPN22 在淋巴细胞的发育和激活、耐受性的建立以及先天免疫细胞介导的宿主防御和免疫调节中发挥作用。疾病相关的 PTPN22-R620W 变异蛋白可能参与自身免疫病发病机制的多个阶段。在未成熟 B 细胞选择过程中，PTPN22-R620W 作用破坏了耐受性 B 细胞库的建立，并且 PTPN22-R620W 改变了成熟 T 细胞的反应性。然而，在自身免疫攻击引发组织损伤后，PTPN22-R620W 可能通过调节骨髓细胞产生的细胞因子的平衡来促进炎症。