A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20's OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20ZF7 mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions. A20ZF7 cells exhibited prolonged IκB kinase activity that drove exaggerated transcription of late-phase nuclear factor-κB response genes in vitro and in prediseased mouse paws in vivo. In addition, mice expressing double-mutant A20 proteins in A20's ZF4 and ZF7 motifs died perinatally with multi-organ inflammation. Therefore, A20's ZF4 and ZF7 motifs synergistically prevent inflammatory disease in a non-catalytic manner.

中文翻译：

---

A20的非催化泛素结合可预防银屑病样关节炎和炎症。

A20是一种抗炎蛋白，与人类疾病密切相关。在这里，我们发现表达A20锌指7（ZF7）泛素结合基序的三个不同的靶向突变的小鼠均匀地发展了具有银屑病关节炎共有特征的指状关节炎，而在A20的OTU或ZF4基序中表达点突变的小鼠则没有这种表型。A20ZF7小鼠的关节炎需要T细胞和MyD88，对肿瘤坏死因子和白介素17A非常敏感，并在无菌条件下持续存在。A20ZF7细胞表现出延长的IκB激酶活性，从而在体外和在体内预先患病的老鼠爪中导致晚期核因子-κB反应基因的转录过度。此外，小鼠在A20'中表达双突变A20蛋白 ZF4和ZF7基序在围产期死于多器官炎症。因此，A20的ZF4和ZF7基序以非催化方式协同预防炎性疾病。