Microgravity-induced alterations in signal transduction in cells of the immune system

Signal Transduction in Primary Human T Lymphocytes in Altered Gravity During Parabolic Flight and Clinostat Experiments

“…P-p44/42 MAPK was also reduced during the hyp-g phase [27]. In a previous study with Jurkat T cells, we detected an enhanced phosphorylation level of p44/42 MAPK in CD3/CD28 stimulated as well as non-stimulated Jurkat T cells after 5 minutes clinorotation and an enhanced phosphorylation level of MEK [15]. During a parabolic flight experiment with 20 seconds real microgravity, we detected an enhanced MEK phosphorylation in stimulated, but not in non-stimulated Jurkat cells [15].…”

“…During space flights and in microgravity analogues, dysregulation of T cell function has been observed in a multitude of studies [7,8,13,14,15,16,17,18,19,20,45,46]. We found a rapid decrease of CD3 and IL-2R surface expression and reduced p-LAT after 20 seconds of altered gravity during parabolic flight, decreased CD3 surface expression, reduced ZAP-70 abundance and increased histone H3-acetylation in activated T lymphocytes after 5 minutes of clinorotation and a transient downregulation of CD3 and stable downregulation of IL-2R during 60 minutes of clinorotation.…”

“…In a previous study with Jurkat T cells, we detected an enhanced phosphorylation level of p44/42 MAPK in CD3/CD28 stimulated as well as non-stimulated Jurkat T cells after 5 minutes clinorotation and an enhanced phosphorylation level of MEK [15]. During a parabolic flight experiment with 20 seconds real microgravity, we detected an enhanced MEK phosphorylation in stimulated, but not in non-stimulated Jurkat cells [15]. The MAPK cascade is a central signal system which is triggered and inhibited by a multitude of intra- and extracellular events and which comprises various negative and positive feedback loops.…”

“…1b). The system has already been used successfully for cell culture experiments during the 8 th , 9 th , 10 th , 13 th , 14 th and 16 th DLR Parabolic Flight Campaigns and during the 45 th ESA Parabolic Flight Campaign [13,15]. The system consists of double-sealed cell containers holding the T lymphocytes and three experimental modules that supply storage of samples before the experiment, half-automated performance of the experiment and storage of the processed samples.…”

“…Many studies have revealed strong effects of microgravity on immune cell function [9,10,11], which were performed during manned space flights, on board of orbital, suborbital (sounding rockets) and parabolic flights, and were supported by ground-based facilities for simulation of microgravity such as clinorotation and 3D-random positioning machines [12]. Gravity-sensitivity in T lymphocytes was found for the cell cycle regulation [13], epigenetic regulation [14], chromatin regulation [15], expression profile of microRNA [16], cell motility [17], regulation of apoptosis [18], expression of cytokines [19], and expression of early genes of T lymphocyte activation, which are regulated primarily by the transcription factors NF-κB, CREB, ELK, AP-1, and STAT [13,20,21]. Taken together, the phenomenon of reduced activation of T cells and alterations in several cellular processes during microgravity is well described.…”