Polyunsaturated fatty acids in the modulation of T-cell signalling

Abstract 

n-3 Polyunsaturated fatty acids (PUFA) have been shown to modulate immune responses. These agents, being considered as adjuvant immunosuppressants, have been used in the treatment of various inflammatory and autoimmune diseases. However, the molecular mechanisms of action of n-3 PUFA-induced immunosuppressive effects are not well-understood. Since exogenous n-3 PUFA, under in vitro and in vivo conditions, are efficiently incorporated into T-cell plasma membranes, a number of recent studies have demonstrated that these agents may modulate T-cell signalling. In this review, the interactions of n-3 PUFA with the second messenger cascade initiated during early and late events of T-cell activation are discussed. We particularly focus on how these fatty acids can modulate the production of diacylglycerol and the activation of protein kinase C, mitogen activated protein kinase, calcium signalling and translocation of transcriptional factors, implicated in the regulation of gene transcription in T-cells.

Abbreviations: CRAC, Ca²⁺ release-activated Ca²⁺ channels, DAG, diacylglycerol, DHA, docosahexaenoic acid, EPA, eicosapentaenoic acid, ER, endoplasmic reticulum, IP₃, inositol trisphosphate, MAPK, mitogen activated protein kinase, PKC, protein kinase C, PLA₂, phospholipase A₂, PLD, phospholipase D, PUFA, polyunsaturated fatty acids, SAG, 1-stearoyl-2-arachidonyl-sn-glycerol, SDG, 1-stearoyl-2-docosahexaenoyl-sn-glycerol, SEG, 1-stearoyl-2-eicosapentaenoyl-sn-glycerol, SOC, store-operated calcium channels