DHA Sensor GPR120 in Host Defense Exhibits the Dual Characteristics of Regulating Dendritic Cell Function and Skewing the Balance of Th17/Tregs
DHA Sensor GPR120 in Host Defense Exhibits the Dual Characteristics of Regulating Dendritic Cell Function and Skewing the Balance of Th17/Tregs
复制标题
宿主防御中的 DHA 传感器 GPR120 具有调节树突状细胞功能和扭曲 Th17/Treg 平衡的双重特性
DOI：
10.7150/ijbs.39551
复制
发表时间：
2020-01
影响因子：
9.2
通讯作者：
Yang Yang
中科院分区：
文献类型：
--
作者：
Zhao Caiquuan;Zhou Jinxiu;Meng Yanqing;Shi Niu;Wang Xiao;Zhou Ming;Li Guangpeng;Yang Yang
除了作为抗氧化剂，抗炎和抗衰老的细胞成分外，DHA还通过促进病原体入侵来影响免疫系统。DHA调节免疫抑制的机制仍然不清楚。在我们的研究中，我们假设DHA可能与GPR 120相互作用，以塑造树突状细胞（DC）分化，并随后在病毒感染期间驱动T细胞增殖。在体外，从外源性和内源性（fad 3b表达）DHA补充小鼠产生的DC上的共刺激分子和HLA-DR的比例显着低于野生型小鼠。考虑到脂肪酸的重要性，DHA不仅是一种关键的细胞成分，也是一种细胞信号分子，FA缺乏会减少DC的产生;我们使用GPR 120-/-小鼠来确定DHA受体缺乏是否会扰乱DC的成熟过程。新奇的是，来自野生型（WT）小鼠的DC上GPR 120的表达与DC活化呈负相关，并且来自GPR 120-/-小鼠的DC维持自发成熟状态。在体内，DHA对GPR 120的过度激活和GPR 120的缺失都有效地扭曲了Th 17/T细胞的平衡，降低了VNA的产生和疫苗的保护作用。总之，我们的研究结果揭示了GPR 120自身调节在感知DHA变化中起关键作用的机制，这为自身免疫性疾病的治疗操作和疫苗佐剂的设计提供了新的前景。
In addition to functioning as an antioxidant, anti-inflammatory and age-defying cellular component, DHA impacts the immune system by facilitating the pathogen invasion. The mechanism through which DHA regulates immune suppression remains obscure. In our study, we postulated that DHA might interact with GPR120 to shape the dendritic cell (DC) differentiation and subsequently drive T cell proliferation during the virus infection. In vitro, the proportion of costimulatory molecules and HLA-DR on DC that generated from exogenous and endogenous (fad3b expression) DHA supplemented mice were significantly lower than wild-type mice. Given the importance of FAs, DHA is not only a critical cellular constituent but also a cell signaling molecule and FA deficiency reduces DC generation; we used GPR120-/- mice to determine whether DHA receptor deficiency disorders DC maturation processing. Novelty, the expression of GPR120 on DC from wild-type (WT) mice was inversely related to DC activation and DC from the GPR120-/- mice maintained a spontaneous maturation status. In vivo, both the excessive activation of GPR120 by DHA and the deletion of GPR120 effectively skewed the balance of Th17/Tregs and reduced the production of VNA and protection of vaccination. Overall, our results revealed a mechanism that the GPR120 self-regulation plays a crucial role in sensing DHA variation, which provides a new prospect for therapeutic manipulation in autoimmune diseases and the design of a vaccine adjuvant.
登录
查看更多内容
DOI：
10.1037/e546412006-001
发表时间：
1991
期刊：
MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.3
作者：
Wellhauser L;Belsham DD
通讯作者：
Belsham DD
欧米茄3多不饱和脂肪酸通过调节FAD3B转基因小鼠胚胎干细胞中的细胞周期来抑制细胞增殖。
影响因子：
4.5
作者：
Wei Z;Li D;Zhu L;Yang L;Chen C;Bai C;Li G
通讯作者：
Li G
影响因子：
1.9
作者：
Varney ME;Buchanan JT;Dementieva Y;Hardman WE;Sollars VE
通讯作者：
Sollars VE
Omega-3 脂肪酸通过抑制 NLRP3 炎症小体激活来预防炎症和代谢紊乱。
影响因子：
32.4
作者：
Yan, Yiqing;Jiang, Wei;Zhou, Rongbin
通讯作者：
Zhou, Rongbin