Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous preclinical studies have shown that the enriched environment (EE) confers anti‐obesity and anti‐cancer phenotypes that are associated with enhanced adaptive immunity and are mediated by brain‐derived neurotrophic factor (BDNF). Natural killer (NK) cells have anti‐cancer and anti‐viral properties, and their absence or depletion is associated with inferior clinical outcomes. In this study, we investigated the effects of EE on NK cell maturation following their depletion. Mice living in EE displayed a higher proportion of NK cells in the spleen, bone marrow, and blood, compared to those living in the standard environment (SE). EE enhanced NK cell maturation in the spleen and was associated with upregulation of BDNF expression in the hypothalamus. Hypothalamic BDNF overexpression reproduced the EE effects on NK cell maturation in secondary lymphoid tissues. Conversely, hypothalamic BDNF knockdown blocked the EE modulation on NK cell maturation. Our results demonstrate that a bio‐behavior intervention enhanced NK cell maturation and was mediated at least in part by hypothalamic BDNF.

中文翻译：

---

丰富的环境通过雄性小鼠下丘脑 BDNF 促进 NK 细胞成熟

宏观环境因素，包括患者的身体和社会环境，在癌症风险和进展中发挥作用。我们之前的临床前研究表明，丰富的环境（EE）赋予抗肥胖和抗癌表型，这些表型与增强的适应性免疫相关，并由脑源性神经营养因子（BDNF）介导。自然杀伤 (NK) 细胞具有抗癌和抗病毒特性，它们的缺失或耗竭与较差的临床结果相关。在这项研究中，我们研究了 EE 在耗尽后对 NK 细胞成熟的影响。与生活在标准环境 (SE) 中的小鼠相比，生活在 EE 中的小鼠在脾脏、骨髓和血液中显示出更高比例的 NK 细胞。EE 增强了脾脏中 NK 细胞的成熟，并与下丘脑中 BDNF 表达的上调有关。下丘脑 BDNF 过表达再现了 EE 对次级淋巴组织中 NK 细胞成熟的影响。相反，下丘脑 BDNF 敲低阻断了 EE 对 NK 细胞成熟的调节。我们的研究结果表明，生物行为干预增强了 NK 细胞成熟，并且至少部分由下丘脑 BDNF 介导。