IL-2 调节 T 细胞分化：低剂量 IL-2 诱导免疫调节性 Treg 分化，而高剂量 IL-2 则充当细胞毒性 T 细胞和 NK 细胞的有效激活剂。因此，高剂量IL-2已被研究用于癌症免疫治疗。我们的目标是利用低剂量 IL-2 来治疗肥胖和胰岛素抵抗等炎症性疾病，这些疾病涉及低度慢性炎症。全身施用低剂量 IL-2 可以增加 Treg 细胞并减少性腺白色脂肪组织中的炎症。 gWAT），从而提高高脂肪饮食喂养的肥胖小鼠的胰岛素敏感性。此外，IL-2 的中枢给药可通过激活交感神经系统显着增强胰岛素敏感性。中枢 IL-2 给药诱导的交感信号传导不仅减少了干扰素 γ (IFNγ)   Th1 细胞和促炎细胞因子（包括 Il-1β、Il-6 和 Il-8）的表达，而且还增加了 CD4   CD25   FoxP3  Treg肥胖小鼠 gWAT 中的细胞和 Tgfβ 表达。这些现象伴随着下丘脑小胶质细胞增生和阿黑皮质素原神经元的激活。此外，gWAT 中的交感神经去神经逆转了中枢 IL-2 给药诱导的胰岛素敏感性增强和免疫细胞极化。总的来说，我们证明 IL-2 通过两种机制提高胰岛素敏感性：直接作用于 CD4  T 细胞和通过神经免疫由下丘脑小胶质细胞增生触发的轴。© 2024。作者。

IL-2 regulates T cell differentiation: low-dose IL-2 induces immunoregulatory Treg differentiation, while high-dose IL-2 acts as a potent activator of cytotoxic T cells and NK cells. Therefore, high-dose IL-2 has been studied for use in cancer immunotherapy. We aimed to utilize low-dose IL-2 to treat inflammatory diseases such as obesity and insulin resistance, which involve low-grade chronic inflammation.Systemic administration of low-dose IL-2 increased Treg cells and decreased inflammation in gonadal white adipose tissue (gWAT), leading to improved insulin sensitivity in high-fat diet-fed obese mice. Additionally, central administration of IL-2 significantly enhanced insulin sensitivity through the activation of the sympathetic nervous system. The sympathetic signaling induced by central IL-2 administration not only decreased interferon γ (IFNγ) + Th1 cells and the expression of pro-inflammatory cytokines, including Il-1β, Il-6, and Il-8, but also increased CD4 + CD25 + FoxP3 + Treg cells and Tgfβ expression in the gWAT of obese mice. These phenomena were accompanied by hypothalamic microgliosis and activation of pro-opiomelanocortin neurons. Furthermore, sympathetic denervation in gWAT reversed the enhanced insulin sensitivity and immune cell polarization induced by central IL-2 administration.Overall, we demonstrated that IL-2 improves insulin sensitivity through two mechanisms: direct action on CD4 + T cells and via the neuro-immune axis triggered by hypothalamic microgliosis.© 2024. The Author(s).