Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Nat Commun. 2019 Mar 4;10(1):1037. doi: 10.1038/s41467-019-08960-1.
IL-2R signaling is essential for regulatory T cell (Treg) function. However, the precise contribution of IL-2 during Treg thymic development, peripheral homeostasis and lineage stability remains unclear. Here we show that IL-2R signaling is required by thymic Tregs at an early step for expansion and survival, and a later step for functional maturation. Using inducible, conditional deletion of CD25 in peripheral Tregs, we also find that IL-2R signaling is indispensable for Treg homeostasis, whereas Treg lineage stability is largely IL-2-independent. CD25 knockout peripheral Tregs have increased apoptosis, oxidative stress, signs of mitochondrial dysfunction, and reduced transcription of key enzymes of lipid and cholesterol biosynthetic pathways. A divergent IL-2R transcriptional signature is noted for thymic Tregs versus peripheral Tregs. These data indicate that IL-2R signaling in the thymus and the periphery leads to distinctive effects on Treg function, while peripheral Treg survival depends on a non-conventional mechanism of metabolic regulation.
IL-2R 信号对于调节性 T 细胞（Treg）的功能至关重要。然而，IL-2 在 Treg 胸腺发育、外周稳态和谱系稳定性中的精确作用仍不清楚。在这里，我们表明，IL-2R 信号在胸腺 Treg 的早期扩张和存活以及后期的功能成熟中是必需的。使用外周 Treg 中 CD25 的诱导性、条件性缺失，我们还发现，IL-2R 信号对于 Treg 的稳态是不可或缺的，而 Treg 谱系的稳定性在很大程度上是不依赖于 IL-2 的。CD25 敲除的外周 Treg 细胞凋亡增加，氧化应激增加，线粒体功能障碍的迹象明显，脂质和胆固醇生物合成途径的关键酶的转录减少。胸腺 Treg 与外周 Treg 的 IL-2R 转录特征明显不同。这些数据表明，胸腺和外周的 IL-2R 信号导致 Treg 功能的独特影响，而外周 Treg 的存活取决于代谢调节的非传统机制。
