CB2 刺激脂肪组织固有 ILC2 可调控免疫平衡并改善 2 型糖尿病。

Suppr 超能文献

核心技术专利：CN118964589B侵权必究

Suppr 超能文献

核心技术专利：CN118964589B侵权必究

Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Cell Rep. 2024 Jul 23;43(7):114434. doi: 10.1016/j.celrep.2024.114434. Epub 2024 Jul 3.

Development of type 2 diabetes mellitus (T2DM) is associated with low-grade chronic type 2 inflammation and disturbance of glucose homeostasis. Group 2 innate lymphoid cells (ILC2s) play a critical role in maintaining adipose homeostasis via the production of type 2 cytokines. Here, we demonstrate that CB, a G-protein-coupled receptor (GPCR) and member of the endocannabinoid system, is expressed on both visceral adipose tissue (VAT)-derived murine and human ILC2s. Moreover, we utilize a combination of ex vivo and in vivo approaches to explore the functional and therapeutic impacts of CB engagement on VAT ILC2s in a T2DM model. Our results show that CB stimulation of ILC2s protects against insulin-resistance onset, ameliorates glucose tolerance, and reverses established insulin resistance. Our mechanistic studies reveal that the therapeutic effects of CB are mediated through activation of the AKT, ERK1/2, and CREB pathways on ILC2s. The results reveal that the CB agonist can serve as a candidate for the prevention and treatment of T2DM.

2 型糖尿病（T2DM）的发展与低水平慢性 2 型炎症和葡萄糖稳态紊乱有关。2 型固有淋巴细胞（ILC2）通过产生 2 型细胞因子在维持脂肪组织稳态方面发挥着关键作用。在这里，我们证明大麻素受体（CB）作为一种 G 蛋白偶联受体（GPCR）和内源性大麻素系统的成员，在来源于内脏脂肪组织（VAT）的鼠类和人类 ILC2 上均有表达。此外，我们利用体外和体内相结合的方法来探索在 T2DM 模型中，CB 对 VAT ILC2 的功能和治疗作用的影响。我们的结果表明，CB 刺激 ILC2 可预防胰岛素抵抗的发生，改善葡萄糖耐量，并逆转已建立的胰岛素抵抗。我们的机制研究表明，CB 的治疗作用是通过激活 ILC2 上的 AKT、ERK1/2 和 CREB 途径来介导的。这些结果表明，CB 激动剂可以作为预防和治疗 T2DM 的候选药物。