de Jong Anja J, Kloppenburg Margreet, Toes René E M, Ioan-Facsinay Andreea
Department of Rheumatology, Leiden University Medical Centre , Leiden , Netherlands.
Front Immunol. 2014 Oct 13;5:483. doi: 10.3389/fimmu.2014.00483. eCollection 2014.
Research toward the mechanisms underlying obesity-linked complications has intensified during the last years. As a consequence, it has become clear that metabolism and immunity are intimately linked. Free fatty acids and other lipids acquired in excess by current feeding patterns have been proposed to mediate this link due to their immune modulatory capacity. The functional differences between saturated and unsaturated fatty acids, in combination with their dietary intake are believed to modulate the outcome of immune responses. Moreover, unsaturated fatty acids can be oxidized in a tightly regulated and specific manner to generate either potent pro-inflammatory or pro-resolving lipid mediators. These oxidative derivatives of fatty acids have received detailed attention during the last years, as they have proven to have strong immune modulatory capacity, even in pM ranges. Both fatty acids and oxidized fatty acids have been studied especially in relation to macrophage and T-cells functions. In this review, we propose to focus on the effect of fatty acids and their oxidative derivatives on T-cells, as it is an active area of research during the past 5 years. The effect of fatty acids and their derivatives on activation and proliferation of T-cells, as well as the delicate balance between stimulation and lipotoxicity will be discussed. Moreover, the receptors involved in the interaction between free fatty acids and their derivatives with T-cells will be summarized. Finally, the mechanisms involved in modulation of T-cells by fatty acids will be addressed, including cellular signaling and metabolism of T-cells. The in vitro results will be placed in context of in vivo studies both in humans and mice. In this review, we summarize the latest findings on the immune modulatory function of lipids on T-cells and will point out novel directions for future research.
在过去几年中，针对肥胖相关并发症潜在机制的研究不断深入。因此，新陈代谢与免疫之间存在密切联系这一点已变得清晰。由于其免疫调节能力，目前饮食模式中过量摄入的游离脂肪酸和其他脂质被认为介导了这种联系。饱和脂肪酸和不饱和脂肪酸之间的功能差异，连同它们的饮食摄入量，被认为会调节免疫反应的结果。此外，不饱和脂肪酸可以通过严格调控的特定方式被氧化，从而产生强效的促炎或促解决脂质介质。在过去几年中，这些脂肪酸的氧化衍生物受到了详细关注，因为它们已被证明即使在皮摩尔范围内也具有强大的免疫调节能力。脂肪酸和氧化脂肪酸都尤其针对巨噬细胞和T细胞功能进行了研究。在本综述中，我们建议聚焦于脂肪酸及其氧化衍生物对T细胞的影响，因为这是过去5年中一个活跃的研究领域。将讨论脂肪酸及其衍生物对T细胞活化和增殖的影响，以及刺激与脂毒性之间的微妙平衡。此外，还将总结游离脂肪酸及其衍生物与T细胞相互作用中涉及的受体。最后，将探讨脂肪酸调节T细胞的机制，包括T细胞的细胞信号传导和代谢。体外研究结果将与人类和小鼠的体内研究情况相结合。在本综述中，我们总结了脂质对T细胞免疫调节功能的最新发现，并将指出未来研究的新方向。
