Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Microbiol Immunol. 2020 Aug;64(8):563-569. doi: 10.1111/1348-0421.12800. Epub 2020 Jun 15.
The present study was to demonstrate that the G protein coupled receptors serve as targets for the treatment of autoimmune disease such as rheumatoid arthritis and multiple sclerosis. Rats received pristane at the base of the tail. Affected joints were counted daily. The T cell mediated autoimmune diseases such as pristine-induced arthritis (PIA) and autoimmune encephalomyelitis (EAE) in a rat model were profoundly ameliorated by treatment with the specific G protein couple receptors 120 (GPR120) stimuli omega-3 fatty acids (ω-3 FAs). Our study further revealed that the activation of GPR120 by ω-3 FAs can result in a decrease of phosphorylated transforming growth factor-β activated kinase 1 (TAK1), and further inhibit the downstream IKKβ/I-κB pathway and the terminal NF-κB activation which serves as a mediator of T cell activation. ω-3 Fatty acids exhibited an inhibitory effect on TAK1 by enhancing the association of β-arrestin2 and TAK1 binding protein 1 (TAB1), thus the disassociation of TAB1 from the TAB1/TAK1 complex renders a limited effect on β-arrestin2 signaling as an innate immunity regulation. GPR120 is a functional receptor of ω-3 fatty acids in T cell-mediated autoimmune disease compared with its effect on innate immunity.
本研究旨在证明 G 蛋白偶联受体可作为治疗类风湿性关节炎和多发性硬化症等自身免疫性疾病的靶点。大鼠在尾根部接受了降植烷处理。每天对受影响的关节进行计数。在大鼠模型中，用特定的 G 蛋白偶联受体 120（GPR120）刺激ω-3 脂肪酸（ω-3 FAs）治疗，可显著改善 T 细胞介导的自身免疫性疾病，如降植烷诱导的关节炎（PIA）和自身免疫性脑脊髓炎（EAE）。我们的研究进一步表明，ω-3 FAs 激活 GPR120 可导致磷酸化转化生长因子-β激活激酶 1（TAK1）减少，进而抑制下游 IKKβ/I-κB 途径和末端 NF-κB 激活，NF-κB 激活作为 T 细胞激活的介质。ω-3 脂肪酸通过增强β-arrestin2 和 TAK1 结合蛋白 1（TAB1）与 TAK1 的结合，对 TAK1 具有抑制作用，从而使 TAB1 从 TAB1/TAK1 复合物中解离，对β-arrestin2 信号的影响有限，作为先天免疫调节。与先天免疫相比，GPR120 是 T 细胞介导的自身免疫性疾病中 ω-3 脂肪酸的功能性受体。
