在过去的几十年里,免疫系统与代谢之间的关系已成为主要的研究热点。在这个免疫代谢领域,脂肪组织分泌免疫调节分子的能力,包括脂肪因子,在肥胖期间潜在的低度炎症引起了人们对肥胖对免疫系统的影响的关注。脂肪因子,如瘦素和脂联素,影响T细胞分化为不同的T辅助细胞亚群及其在免疫应答过程中的激活。此外,在脂肪组织的细胞环境中,营养可利用性调节T细胞的分化和活化以及细胞代谢途径的变化。激活后,T细胞从氧化磷酸化转变为氧化糖酵解,而激酶哺乳动物雷帕霉素靶蛋白(mTOR)和核受体PPARγ的差异信号,在其他人中,驱动随后的T细胞分化。虽然导致肥胖期间从典型的2型主导环境转变为Th1型偏向促炎环境的机制是广泛研究的主题,关于其对外周Th2主导的免疫反应的影响的见解变得更加明显。在这次审查中,我们将总结最近关于Th2细胞在肥胖和营养不良过程中如何代谢调节的发现,以及这些状态如何影响局部和全身Th2-偏向的免疫反应。
Over the past decades, the relationship between the immune system and metabolism has become a major research focus. In this arena of immunometabolism the capacity of adipose tissue to secrete immunomodulatory molecules, including adipokines, within the underlying low-grade inflammation during obesity brought attention to the impact obesity has on the immune system. Adipokines, such as leptin and adiponectin, influence T cell differentiation into different T helper subsets and their activation during immune responses. Furthermore, within the cellular milieu of adipose tissue nutrient availability regulates differentiation and activation of T cells and changes in cellular metabolic pathways. Upon activation, T cells shift from oxidative phosphorylation to oxidative glycolysis, while the differential signaling of the kinase mammalian target of rapamycin (mTOR) and the nuclear receptor PPARγ, amongst others, drive the subsequent T cell differentiation. While the mechanisms leading to a shift from the typical type 2-dominated milieu in lean people to a Th1-biased pro-inflammatory environment during obesity are the subject of extensive research, insights on its impact on peripheral Th2-dominated immune responses become more evident. In this review, we will summarize recent findings of how Th2 cells are metabolically regulated during obesity and malnutrition, and how these states affect local and systemic Th2-biased immune responses.