Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, Leioa, Spain.
Faculty of Sport Sciences, European University of Madrid, Madrid, Spain.
Exerc Immunol Rev. 2021;27:125-141.
Regular exercise, particularly moderate-intensity continuous training (MICT), can improve immune function. Natural killer (NK) cells, a subset of lymphocytes that react to infections, are the most responsive innate immune cells to exercise, but the mechanisms underlying this are poorly understood. A type of exercise training that is gaining popularity in recent years is high-intensity interval training (HIIT), but how it affects NK cells is largely unknown. In fact, intense exercise has been traditionally viewed as a potential stressor to immune homeostasis. The purpose of this study was to determine in healthy, previously untrained adults (N=8 [3 male; 40±6 years]) the effects of an intervention consisting of 4-week MICT followed by 4-week HIIT on NK cells as compared with a pre-training (baseline) state.
Participants were studied at three time points: baseline, mid-intervention (after MICT), and post-intervention (after HIIT). Main assessments included cytotoxicity assays, flow-cytometry analysis of NK cell surface markers, and interrogation of the cellular proteome using a systems biology approach.
A significant time effect was found for NK cell cytotoxicity (p<0.001), which was increased ~10-fold at both midand post-intervention versus baseline. No significant intervention effect was found for NK surface receptor expression, except for CXCR3 determined as mean fluorescence intensity (p=0.044, although with no significant differences in post hoc pairwise comparisons). The proteins showing a higher differential expression (Log2 fold-change > 10 and false discovery rate [FDR] q-value < 0.001) were COP9 signalosome subunit 3 (COPS3), DnaJ heat shock protein family member B11 (DNAJB11), histidyl-TRNA synthetase 1 (HARS), NIMA related kinase 9 (NEK9), nucleoporin 88 (NUP88), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), regulator of chromosome condensation 2 (RCC2), TAO kinase 3 (TAOK3), transducin beta like 2 (TBL2), and ring finger protein 40 (RNF40). All were upregulated at mid-intervention compared with baseline, with the exception of HARS, which was downregulated. Four enriched pathways (FDR p<25%) were found: two related to transmembrane transport and cellular composition (downregulated at mid-intervention vs baseline), and two related to oxidation- reduction reactions (regulated at post-intervention versus baseline).
A progressive exercise intervention of MICT followed by HIIT induces a remarkable improvement in NK function compared with the untrained state, although at the mechanistic level the pathways involved seem to differ over time during the intervention.
有规律的运动，特别是中等强度的持续训练（MICT），可以改善免疫功能。自然杀伤（NK）细胞是对感染产生反应的淋巴细胞亚群之一，是对运动反应最敏感的固有免疫细胞，但运动对其影响的机制尚不清楚。近年来，一种越来越受欢迎的运动训练方式是高强度间歇训练（HIIT），但它如何影响 NK 细胞在很大程度上仍是未知的。事实上，剧烈运动一直被传统上视为对免疫稳态的潜在应激源。本研究的目的是在健康的、未经训练的成年人（N=8[3 名男性；40±6 岁]）中确定，与训练前（基线）状态相比，4 周的 MICT 加 4 周的 HIIT 干预对 NK 细胞的影响。
参与者在三个时间点进行研究：基线、干预中期（MICT 后）和干预后（HIIT 后）。主要评估包括细胞毒性测定、NK 细胞表面标志物的流式细胞术分析以及使用系统生物学方法检测细胞蛋白质组。
发现 NK 细胞细胞毒性有显著的时间效应（p<0.001），与基线相比，中期和后期干预时 NK 细胞细胞毒性分别增加了约 10 倍。NK 表面受体表达没有显著的干预效应，除了 CXCR3 作为平均荧光强度（p=0.044，尽管在后测配对比较中没有显著差异）。表现出更高差异表达（Log2 倍数变化>10，错误发现率[FDR]q 值<0.001）的蛋白质是 COP9 信号体亚基 3（COPS3）、DNAJ 热休克蛋白家族成员 B11（DNAJB11）、组氨酸 tRNA 合成酶 1（HARS）、NIMA 相关激酶 9（NEK9）、核孔蛋白 88（NUP88）、磷酸肌醇-3-激酶调节亚基 1（PIK3R1）、染色体凝聚调节因子 2（RCC2）、TAO 激酶 3（TAOK3）、转导素β样 2（TBL2）和环指蛋白 40（RNF40）。与基线相比，所有这些蛋白质在中期干预时均上调，除了 HARS 下调。发现了四个富集途径（FDR p<25%）：两个与跨膜转运和细胞组成有关（中期干预时下调），两个与氧化还原反应有关（干预后上调）。
与未经训练状态相比，MICT 后加 HIIT 的渐进性运动干预可显著改善 NK 功能，尽管在机制水平上，在干预过程中，不同时间涉及的途径似乎有所不同。
