Differential effects of hypergravity on immune dysfunctions induced by simulated microgravity. Issue 5 (18th April 2023)

• Record Type: Journal Article
• Authors: Moser, Dominique; Biere, Katharina; Liemersdorf, Christian; Tuschen, Marina; Hemmersbach, Ruth; Choukér, Alexander
• Is Part Of: FASEB journal. Volume 37:Issue 5(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-04-18
• Subjects: artificial gravity -- clinostat -- cytokines -- hypergravity -- microgravity -- monocytes -- preconditioning -- T cells; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202201781R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Microgravity (μ g ) 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 μ g ‐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 μ g ‐mediated immune dysregulations. For this, T cell and monocyte activation states and cytokine pattern were first analyzed after whole blood antigen incubation in simulated μ g (s‐μ g ) 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‐μ g exposure and two therapeutic approaches in which 2.8 g was set either intermediately or at the end of s‐μ g . In single g ‐grade exposure experiments, monocyte pro‐inflammatory state was enhanced in s‐μ g and reduced in hypergravity, whereas T cells displayed reduced activation when antigen incubation was performed in s‐μ g . 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‐)μ g and that it may act as a booster of immune cell functions. Abstract : This study represents a proof of concept showing the potential of hypergravity to counteract microgravity‐induced immune cell dysregulations. For this, human whole blood was incubated ex vivo with immunogenic stimuli in normogravity (1 g ), simulated microgravity (s‐μ g ) or with a hypergravity (2.8 g ) intervention. Results demonstrate reduced T cell activation capacities (CD69 expression and cytokine secretion) in s‐μ g, which were restored by hypergravity preconditioning. Monocytes show an increased pro‐inflammatory potential in s‐μ g which was not further affected by additional hypergravity exposure.