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DHA 传感器 GPR120 在宿主防御中表现出调节树突状细胞功能和偏向 Th17/Treg 平衡的双重特征。

DHA Sensor GPR120 in Host Defense Exhibits the Dual Characteristics of Regulating Dendritic Cell Function and Skewing the Balance of Th17/Tregs.

机构信息

The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, 010070, China.

Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, CN 010017.

出版信息

Int J Biol Sci. 2020 Jan 1;16(3):374-387. doi: 10.7150/ijbs.39551. eCollection 2020.

Abstract

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. , the proportion of costimulatory molecules and HLA-DR on DC that generated from exogenous and endogenous ( 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. , 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.

摘要

除了作为一种抗氧化剂、抗炎和抗衰老的细胞成分外,DHA 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尚不清楚。在我们的研究中,我们假设 DHA 可能与 GPR120 相互作用,塑造树突状细胞 (DC) 的分化,进而在病毒感染期间驱动 T 细胞增殖。从外源性和内源性(表达)DHA 补充的小鼠中产生的 DC 上的共刺激分子和 HLA-DR 的比例明显低于野生型小鼠。鉴于 FAs 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,并且 FA 缺乏会减少 DC 的产生;我们使用 GPR120 小鼠来确定 DHA 受体缺乏是否会干扰 DC 成熟处理。新颖的是,来自野生型 (WT) 小鼠的 DC 上 GPR120 的表达与 DC 的激活呈负相关,并且来自 GPR120 小鼠的 DC 保持自发成熟状态。总之,DHA 对 GPR120 的过度激活和 GPR120 的缺失有效地改变了 Th17/Treg 的平衡,并减少了 VNA 的产生和疫苗接种的保护。总体而言,我们的研究结果揭示了一种机制,即 GPR120 的自我调节在感知 DHA 变化方面起着至关重要的作用,为自身免疫性疾病的治疗干预和疫苗佐剂的设计提供了新的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f48f/6990895/885d83b0ec4b/ijbsv16p0374g001.jpg

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