Lipo-hitting T-cell receptors


Dietary fish oil enriched in n − 3 PUFA has been shown through clinical and epidemiological studies to have anti-inflammatory properties that are beneficial in chronic inflammatory conditions, such as suppression of T-cell activation. Some proposed mechanisms by which n − 3 PUFA suppress T-cell activation include modulation of (i) prostaglandin metabolism, (ii) nuclear transcription factors such as NF-κ B and (iii) plasma membrane microdomains.

Lipid rafts in the plasma membrane are highly enriched in cholesterol and sphingolipids. These domains reside in the Lo (liquid-ordered) phase, and are thought to be critical in CD4+ T-cell activation, where the interaction between MHC II and the TCR (T-cell receptor) on the surface of the APC (antigen-presenting cell) and the T-cell respectively results in the major reorganization of the nanoscale lipid rafts, forming the immunological synapse.

The reconfiguration of lipid rafts to form the immunological synapse involves changes to lipid–lipid interactions in the membranes; specifically, Lo lipids, such as cholesterol and sphingolipids, accumulate at the synapse. The importance of lipid–lipid interactions at the synapse is highlighted by studies demonstrating that dietary n − 3 PUFA can alter the coalescence of lipid rafts.

Many of the actin-remodelling proteins are regulated by PtdIns(4,5)P2. Both the magnitude and the kinetics of PtdIns(4,5)P2 metabolism are important in actin remodelling. Since PtdIns(4,5)P2 co-localizes in raft domains in T-cells, and n − 3 PUFA can alter lipid rafts, PtdIns(4,5)P2 is thought to be perturbed by the presence of n − 3 PUFA, leading to a suppression of downstream actin remodelling.

Hou T. and co-workers (2012) demonstrated for the first time that PtdIns(4,5)P2 is decreased in the presence of n − 3 PUFA in unstimulated CD4 + T-cells, leading to defective PtdIns(4,5)P2 metabolism upon stimulation. The paper demonstrate for the first time that n − 3 PUFA modulate a critical lipid mediator, PtdIns(4,5)P2 , leading to downstream suppression of actin remodelling upon T-cell activation.

Happy Culturing!!!

Remembrane’s Team

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