Laboratory of Translational Research 'Stress and Immunity', Department of Anesthesiology, LMU Hospital, Ludwig-Maximilian-University, Munich, Germany.
Gravitational Biology, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.
FASEB J. 2023 May;37(5):e22910. doi: 10.1096/fj.202201781R.
Microgravity (μg) is among the major stressors in space causing immune cell dysregulations. These are frequently expressed as increased pro-inflammatory states of monocytes and reduced activation capacities in T cells. Hypergravity (as artificial gravity) has shown to have beneficial effects on the musculoskeletal and cardiovascular system both as a countermeasure option for μg-related deconditioning and as "gravitational therapy" on Earth. Since the impact of hypergravity on immune cells is sparsely explored, we investigated if an application of "mild" mechanical loading of 2.8 g is able to avoid or treat μg-mediated immune dysregulations. For this, T cell and monocyte activation states and cytokine pattern were first analyzed after whole blood antigen incubation in simulated μg (s-μg) by using the principle of fast clinorotation or in hypergravity. Subsequent hypergravity countermeasure approaches were run at three different sequences: one preconditioning setting, where 2.8 g was applied before s-μg exposure and two therapeutic approaches in which 2.8 g was set either intermediately or at the end of s-μg. In single g-grade exposure experiments, monocyte pro-inflammatory state was enhanced in s-μg and reduced in hypergravity, whereas T cells displayed reduced activation when antigen incubation was performed in s-μg. Hypergravity application in all three sequences did not alleviate the increased pro-inflammatory potential of monocytes. However, in T cells the preconditioning approach restored antigen-induced CD69 expression and IFNγ secretion to 1 g control values and beyond. This in vitro study demonstrates a proof of concept that mild hypergravity is a gravitational preconditioning option to avoid adaptive immune cell dysfunctions induced by (s-)μg and that it may act as a booster of immune cell functions.
微重力（μg）是太空环境中的主要应激源之一，会导致免疫细胞失调。这些失调通常表现为单核细胞的促炎状态增加和 T 细胞的激活能力降低。超重力（如人工重力）已被证明对肌肉骨骼和心血管系统具有有益影响，既是针对μg 相关失调的对策选择，也是地球上的“重力量疗法”。由于超重力对免疫细胞的影响尚未得到充分探索，我们研究了应用“轻度”机械加载 2.8g 是否能够避免或治疗μg 介导的免疫失调。为此，我们首先通过快速倾斜旋转原理分析了全血在模拟μg（s-μg）中的抗原孵育后 T 细胞和单核细胞的激活状态和细胞因子模式，然后在超重力下进行分析。随后，进行了三种不同顺序的超重力对策方法：一种是预处理设置，即在 s-μg 暴露前应用 2.8g；两种是治疗方法，其中 2.8g 分别在 s-μg 中间或结束时应用。在单 g 级暴露实验中，s-μg 中单核细胞的促炎状态增强，超重力中降低，而抗原孵育时 T 细胞的激活减少。在所有三种顺序中应用超重力均不能减轻单核细胞促炎潜力的增加。然而，在 T 细胞中，预处理方法将抗原诱导的 CD69 表达和 IFNγ 分泌恢复到 1g 对照值及以上。这项体外研究证明了一个概念，即轻度超重力是一种避免（s-）μg 诱导的适应性免疫细胞功能障碍的重力预处理选择，并且它可能作为免疫细胞功能的增强剂。
