Table 5.
Changes in gene regulation of immune system components exposed to microgravity conditions.
| Cell Type | Gene Regulation | Microgravity | Reference |
|---|---|---|---|
| Mouse splenic dendritic cells and mouse Flt-3L-differentiated BMDCs | Downregulation of IL6, IL1B, IL12B, and CXCL10 | s-µg on an RPM for 24 h | [130] |
| Human blood plasma and peripheral blood mononuclear cells from astronauts | Significant increase in cell-free mitochondrial DNA with high variability (between 2- and 355-fold); IL6, IL8, SOD1, SOD2, GPX1, NOX4, GADD45, CAT1, DNA-PK, and PARP1 elevated in at least 1 of the postflight time points | r-µg on the ISS for 5–13 d | [131] |
| Whole blood samples from astronauts | The most commonly mutated gene was TP53 (7 variants) followed by DNTM3A (6 variants) accounting for 38% of mutations detected | r-µg on the ISS (median 12 d) | [132] |
| Human plasma from two male monozygotic twins, one on Earth, one in space (NASA Twins study) | Significant increase in the proportion of cell-free mitochondrial DNA over time |
r-µg on the ISS for 340 d | [133] |
| Humans blood from two male monozygotic twins, one on Earth, one in space (NASA Twins study) | IL-6, TNFR1, and TNFR2 non-canonical NF-kB pathways were affected | r-µg on the ISS for 340 d | [134] |
| Human blood from two male monozygotic twins, one on Earth, one in space (NASA Twins study) | No persistent alteration of long-chain fatty acid desaturase and elongase gene expression associated with 1 year in space | r-µg on the ISS for 340 d | [135] |
| Human Jurkat T cells | 5 µg-sensitive transcript clusters: G3BP1, KPNB1, NUDT3, POMK, SFT2D2 | r-µg on a sounding rocket for 5 min and s-µg on a clinostat for 5 min | [136] |
| Human cell line U937 and human Jurkat T cells |
HIF1A was differently regulated in early response to altered gravity, quick adaption of HIF-1α-dependent gene expression (only IL1B continuously downregulated under µg and SERPINE1, PDK1, and SLC2A3 continuously upregulated under hyper-g) |
r-µg on a parabolic flight for 20 s and r-µg on a sounding rocket for 5 min | [137] |
| Human Jurkat T cells | Gene expression upregulation in chromosome 18 and downregulation in chromosome 19 for all alterations of r-µg conditions | r-µg on a parabolic flight for 20 s, r-µg on a sounding rocket for 5 min, and s-µg on a clinostat for 5 min | [138] |
| Human myelomonocytic U937 cells and human Jurkat T cells | U937 cells: differentially regulated transcripts during parabolic flight and sounding rocket missions: CYBA, PTGS1, PXDN, and ALOX12, GCLM, GSR, MSRA, MT3, OXSR1, PRDX4, PRNP, PTGS2, SELS, SOD1, respectively. Jurkat T cells: no response of oxidative stress-related transcripts to altered gravity |
r-µg on a parabolic flight for 20 s, r-µg on a sounding rocket for 5 min | [139] |
| Human Jurkat T cells | 5 transcripts found to be gravity-regulated in both independent experiments: ATP6V1A, ATP6V1D, IGHD3-3, IGHD3-10, LINC00837 | r-µg on a parabolic flight for 20 s, r-µg on a sounding rocket for 5 min | [140] |
| Mouse hematopoietic progenitor cells | Downregulation of genes of the RAS/ERK/NFκB signaling pathways | r-µg on the Tianzhou-1 cargo ship for 12 days and r-µg on the SJ-10 recoverable satellite for 12 d | [67] |
| Male C57BL/6 J mice | Downregulation of GATA1 and Tal1, downregulation of GATA and Tal1-mediated transcripts | r-µg on the ISS for 35 d | [95] |
| Female C57BL/6J mice | Selected genes involved in glycogen metabolism: Foxo1, Gbe1, Gys2, Ppp1cb, Ppp1ca, Gsk3b, Pck1 upregulated; Pygl downregulated | r-µg on Space Shuttle mission STS-135 for 13 d | [141] |
| Human Jurkat T cells | Resting T cells: FLT1, OTULIN, GPBP1L1, TP53BP1, STK38, PDS5A, PIK3R4, ABCC5, BRWD3, HSPH1, BRD8, NAPB, SLC5A3 upregulated; CXCR3, RBM3, C19orf60, APOBEC2C, SNHG11, SNHG17, ASPSCR1, SFXN2, DCAF16 downregulated Activated T cells: KDM58 upregulated; RBM3, HES1, CXCR3, TUBA4A, HCST, ARID5A, LIMD2, YRDC, LY9, APOBEC3C, LANCL2, RNASEH1, STT3B, PHF7 downregulated |
s-µg on an RPM for 24 h | [142] |
| Murine macrophage RAW 264.7 cells | M0 phenotype: Cd86, Actb upregulated, Arg1 downregulated M1 phenotype: Cd86, Mrc1, Actb upregulated M2 phenotype: Cd86, Mrc1, Arg1, Actb upregulated |
s-µg on an RWV for 3 d | [143] |
| Human peripheral blood mononuclear cells | s-mg decreased effects of 1.5 h-long ConA/anti-CD28 stimulation on IL2RA, TNFA, CD69, and CCL4 | s-µg on a HARV for 18 h | [144] |
| Human peripheral blood lymphocytes | 230 dysregulated transcription factor and microRNA feed-forward loops were found in µg including immune, cardiovascular, endocrine, nervous, and skeletal system subnetworks | s-µg on an RWV for 24 h | [145] |
| Human peripheral blood mononuclear cells | The Radio Electric Asymmetric Conveyer technology could increase IL2 and IL2R gene expression under s-µg | s-µg on an RPM for 2, 4 and 12 h | [146] |
| Human peripheral blood mononuclear cells | BAX, CASP3, PCNA, LIG4, and MDM2 were positively correlated with all cytokines, expressions of AKT1, TP53, PARP1, OGG1, and APXE1 were negatively correlated with these cytokines | s-µg on an RWV for 24 h (+10μM (-)-isoproterenol hydrochloride and/or 0.8 or 2 Gy radiation) | [147] |
| Female C57BL/6J mice | Top 5 upregulated: Slc22a4, Wt1os, 1700063H04Rik, Eral1, Zfp341 Top 4 downregulated: Tmem161b, Prrc1, Kbtbd8, Gm33989, Vps39 |
s-µg by hindlimb unloading + 0.04 Gy irradiation | [148] |
| Danio rerio embryos | Both RLR and TLR signaling pathways were enriched with upregulated genes upon poly(I:C) stimulation and enriched with downregulated genes under s-µg conditions (trim25, nlrx1, traf6, and traf2a and traf6, tlr7, respectively) | s-µg on an RCCS for 24 h | [149] |
Abbreviations: Bone marrow dendritic cells (BMDCs); days (d); high aspect ratio vessels (HARV); head-down tilt (HDT); hours (h); International Space Station (ISS); random positioning machine (RPM); real microgravity (r-µg); rotating cell culture system (RCCS); Rotating wall vessel (RWV); simulated microgravity (s-µg); three-dimensional (3D).