The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China.
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Neuroscience. 2019 Mar 1;401:59-72. doi: 10.1016/j.neuroscience.2019.01.002. Epub 2019 Jan 11.
Depression or stress is reportedly related to the overflow of inflammatory factors in the body and T cells were reported to play important roles in balancing the release of inflammatory factors through vagus nerve circuit. However, few works have been conducted to find if natural killer (NK) cells can also exert the similar function in the reported vagus nerve circuit as T cells and if there was any relationship between depression and this function. In the present study, the behavioral tests on BALB/c mice indicated that the depressant-like symptoms could be improved and simultaneously the concentrations of inflammatory factors in peripheral blood could be reduced significantly by adoptively transferring NK cells into stressed BALB/c mice. The results revealed that NK cells could control the release of inflammatory factors secreted by macrophages and β-AR (β-adrenergic receptor) on the NK cells were of great importance. Behavioral tests on NCG mice indicated that the antidepressant-like effects of NK cells notably declined after adoptively transferring NK cells with β-AR deficiency or with ChAT (choline acetyltransferase) deficiency into stressed NCG mice. Simultaneously, the anti-inflammatory effects also declined significantly both in vivo and in vitro, which indicated that the antidepressant-like property of NK cells may be related to its ability of controlling the release of inflammatory factors. Taken together, we find that NK cells may balance the release of inflammatory factors in our body by transporting the information between the terminal vagal branches and macrophages, which is the mechanism that NK cells may exert antidepressant-like effects.
据报道,抑郁或压力与体内炎症因子的溢出有关,T 细胞被报道通过迷走神经回路在平衡炎症因子的释放方面发挥重要作用。然而,很少有研究发现自然杀伤 (NK) 细胞是否也可以在报道的迷走神经回路中发挥与 T 细胞类似的功能,以及抑郁与这种功能之间是否存在任何关系。在本研究中,对 BALB/c 小鼠的行为测试表明,通过过继转移 NK 细胞到应激的 BALB/c 小鼠中,可以改善抑郁样症状,同时显著降低外周血中炎症因子的浓度。结果表明,NK 细胞可以控制巨噬细胞分泌的炎症因子的释放,而 NK 细胞上的β-AR(β-肾上腺素能受体)非常重要。对 NCG 小鼠的行为测试表明,过继转移 NK 细胞缺乏β-AR 或 ChAT(胆碱乙酰转移酶)缺乏到应激的 NCG 小鼠中后,NK 细胞的抗抑郁样作用明显下降。同时,体内和体外的抗炎作用也明显下降,这表明 NK 细胞的抗抑郁样特性可能与其控制炎症因子释放的能力有关。综上所述,我们发现 NK 细胞可能通过在末梢迷走神经分支和巨噬细胞之间传递信息来平衡体内炎症因子的释放,这是 NK 细胞发挥抗抑郁样作用的机制。