Laboratory of Autoimmunity, The Medical College of Xiamen University, Xiamen University, 361005 Xiamen, China.
Priority Area Asthma and Allergy, Research Center Borstel, 23845, Borstel, Germany.
Autoimmun Rev. 2014 Mar;13(3):266-71. doi: 10.1016/j.autrev.2013.10.011. Epub 2013 Nov 1.
Protein tyrosine phosphatase nonreceptor 22 (PTPN22) represents a strong susceptibility gene which is shared by many autoimmune diseases. Exploring the mechanism behind this association could help to understand their pathogenesis as well as to identify novel therapeutical targets. Recently, multiple mouse models including knock-out, knock-in, knock-down and transgenic mice were generated to delineate PTPN22s function in this context. Depending on the genetic background, mouse PTPN22_619W mutation results in spontaneous autoimmunity, essentially replicating the risk effect of the PTPN22_620W in human autoimmune diseases. Furthermore, findings from mouse models shed new light on both cellular as well as molecular mechanisms of the effect of PTPN22 on adaptive and innate immunity. Here we review recently emerged evidence of the interconnection between mouse PTPN22 and autoimmunity. We also discuss the consistence and discrepancy between findings derived from human and mouse studies.
蛋白酪氨酸磷酸酶非受体 22（PTPN22）是许多自身免疫性疾病共同的强易感基因。探讨这种关联背后的机制有助于了解其发病机制以及确定新的治疗靶点。最近，已经生成了包括敲除、敲入、敲低和转基因在内的多种小鼠模型，以描绘 PTPN22 在这种情况下的功能。根据遗传背景的不同，小鼠 PTPN22_619W 突变导致自发性自身免疫，基本上复制了 PTPN22_620W 在人类自身免疫性疾病中的风险效应。此外，来自小鼠模型的研究结果为 PTPN22 对适应性和固有免疫的影响的细胞和分子机制提供了新的认识。在这里，我们综述了最近出现的关于小鼠 PTPN22 与自身免疫之间相互关系的证据。我们还讨论了源自人类和小鼠研究的结果的一致性和差异。
