The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator–activated receptor β/δ (PPARβ/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8 + T cells. PPARβ/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARβ/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARβ/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity.

中文翻译：

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PPARβ/δ 协调的代谢重编程支持记忆 CD8 + T 细胞的形成和维持


记忆T细胞的形成是适应性免疫的一个基本特征，可以建立针对病原体的长期保护。尽管新的证据表明代谢重编程对于记忆 T 细胞的分化和存活至关重要，但驱动记忆 T 细胞代谢重连的潜在机制仍不清楚。在这里，我们发现核受体过氧化物酶体增殖物激活受体 β/δ (PPARβ/δ) 的上调指导中央记忆 CD8 + T 细胞建立过程中发生的代谢重编程。 PPARβ/δ 调节的变化包括有氧糖酵解的抑制以及氧化代谢和脂肪酸氧化的增强。从机制上讲，暴露于白细胞介素 15 和 T 细胞因子 1 的表达促进了 PPARβ/δ 途径的激活，抵消了抗原清除和代谢应激诱导的细胞凋亡。总之，我们的研究结果表明 PPARβ/δ 是一个主要的代谢调节因子，协调代谢开关，可能有利于 T 细胞的寿命。