Int J Biol Sci 2020; 16(3):374-387. doi:10.7150/ijbs.39551
DHA Sensor GPR120 in Host Defense Exhibits the Dual Characteristics of Regulating Dendritic Cell Function and Skewing the Balance of Th17/Tregs
1. The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, 010070, China
2. The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
3. Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, CN 010017
Zhao C, Zhou J, Meng Y, Shi N, Wang X, Zhou M, Li G, Yang Y. DHA Sensor GPR120 in Host Defense Exhibits the Dual Characteristics of Regulating Dendritic Cell Function and Skewing the Balance of Th17/Tregs. Int J Biol Sci 2020; 16(3):374-387. doi:10.7150/ijbs.39551. Available from http://www.ijbs.com/v16p0374.htm
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.
Keywords: DHA, GPR120, dendritic cell, Th17/Tregs, rabies virus, Japanese encephalitis virus