Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest Agriculture and Forestry (A&F) University, Yangling, China.
Front Immunol. 2022 Aug 12;13:900243. doi: 10.3389/fimmu.2022.900243. eCollection 2022.
Toll-like receptors (TLRs) are involved in the sensing of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), flagellin, unmethylated double-stranded DNA (CpG), single-stranded RNA (ssRNA) and lipoproteins. Myeloid differentiation primary response protein 88 (MyD88) is a canonical adaptor for the Toll-like receptor family which has crucial roles in host defense against infection by microbial pathogens. The dysregulation of MyD88 may also induce autoimmune diseases. Here, we demonstrate that the deubiquitinase USP7 interacts with MyD88 in chicken, with knockdown or overexpression of USP7 leading to the regulation of MyD88 protein in a positive manner. Consequently, USP7 positively regulates the expression of proinflammatory factors upon LPS challenge. Furthermore, we observed USP7-deficient mice to be more susceptible to infection by Salmonella typhimurium. Collectively, our findings demonstrate MyD88 as a bona fide substrate of USP7 and uncover a mechanism by which USP7 regulates innate immune signaling.
Toll 样受体（TLRs）参与识别病原体相关分子模式（PAMPs），如脂多糖（LPS）、鞭毛蛋白、未甲基化双链 DNA（CpG）、单链 RNA（ssRNA）和脂蛋白。髓样分化初级反应蛋白 88（MyD88）是 Toll 样受体家族的一种典型衔接蛋白，在宿主防御微生物病原体感染中起着至关重要的作用。MyD88 的失调也可能导致自身免疫性疾病。在这里，我们证明去泛素化酶 USP7 在鸡中与 MyD88 相互作用，USP7 的敲低或过表达以正向方式调节 MyD88 蛋白。因此，USP7 正向调节 LPS 刺激后促炎因子的表达。此外，我们观察到 USP7 缺陷型小鼠更容易感染鼠伤寒沙门氏菌。总的来说，我们的研究结果表明 MyD88 是 USP7 的真正底物，并揭示了 USP7 调节先天免疫信号的机制。
